Abnormal immune function of B lymphocyte in peripheral blood of Parkinson's disease.

BACKGROUND: Parkinson's disease (PD) is associated with peripheral inflammation and abnormal peripheral blood lymphocyte immune responses. Peripheral blood B-lymphocyte subset distributions and whether they are associated with PD are unclear. METHODS: Sixty-one PD patients and sixty-one one-to-one paired healthy controls (HCs) were enrolled. We used flow cytometry to perform immunophenotyping of peripheral B-lymphocyte, in vitro stimulation and measured serum cytokine. The relationship between variables and PD were assessed. RESULTS: The percentage of naive B cells in blood of PD patients was decreased, whereas the percentages of regulatory B cells (Bregs), plasma blast cells (PBCs), and double-negative (DN) B cells were increased. The absolute counts of B-lymphocyte and naive B cells in blood of PD patients were decreased. Regression analysis revealed that alterations in the absolute counts of B-lymphocyte and the percentage of Bregs and DN B cells were associated with PD. After stimulation, the percentages of Bregs, PBCs, and switched memory (SwM) B cells increased in PD patients. Additionally, increases in GM-CSF-producing B-cell, IFN-γ-producing B-cell, and TNF-α-producing B-cell percentages were noted in PD. Serum levels of a proliferation-inducing ligand (APRIL), B-cell activating factor (BAFF) and soluble CD40 ligand (sCD40L) were elevated in PD and correlated negatively with the UPDRS III score. CONCLUSIONS: Abnormal B-lymphocyte immune responses in peripheral blood may contribute to PD development. Alterations in the absolute counts of B-lymphocyte and the percentage of Bregs and DN B cells are associated with PD. Furthermore, APRIL, BAFF, and sCD40L could be potential targets for intervention in PD.

Impact of B Cell Depletion on COVID-19 in Kidney Transplant Recipients.

Kidney transplant recipients are patients at high risk for coronavirus disease 2019 (COVID-19) due to being on immunosuppressive therapy. B cell depletion therapy, including rituximab, is an important strategy for ABO-incompatible transplants. However, knowledge about the effect of B cell depletion therapy on COVID-19 is lacking. Thirty kidney transplant recipients who developed COVID-19 were included in this study. To examine the impact of B cell depletion therapy, we retrospectively investigated the relationship between the background of the patients and the clinical outcome. Of the 30 patients, 13 received B cell depletion therapy. The median time between transplant and onset of COVID-19 was 6.1 years after transplantation; however, nine cases remained markedly depleted of CD19(+) cells (<4.0%). The patients were assigned to the normal (n = 21) and depletion groups (n = 9). Progression rates in the depletion and normal groups were 55.6% and 9.5%, respectively (p = 0.014). Furthermore, the survival rate was significantly lower in the depletion group (100% in the normal group vs. 66.7% in the depletion group; p = 0.021). B cell depletion therapy may have long-term effects and increase the risk of COVID-19 in kidney transplant recipients.

An Optimized Flow Cytometric Method to Demonstrate the Differentiation Stage-Dependent Ca2+ Flux Responses of Peripheral Human B Cells.

Calcium (Ca2+) flux acts as a central signaling pathway in B cells, and its alterations are associated with autoimmune dysregulation and B-cell malignancies. We standardized a flow-cytometry-based method using various stimuli to investigate the Ca2+ flux characteristics of circulating human B lymphocytes from healthy individuals. We found that different activating agents trigger distinct Ca2+ flux responses and that B-cell subsets show specific developmental-stage dependent Ca2+ flux response patterns. Naive B cells responded with a more substantial Ca2+ flux to B cell receptor (BCR) stimulation than memory B cells. Non-switched memory cells responded to anti-IgD stimulation with a naive-like Ca2+ flux pattern, whereas their anti-IgM response was memory-like. Peripheral antibody-secreting cells retained their IgG responsivity but showed reduced Ca2+ responses upon activation, indicating their loss of dependence on Ca2+ signaling. Ca2+ flux is a relevant functional test for B cells, and its alterations could provide insight into pathological B-cell activation development.

Effective Treatment of Patients Experiencing Primary, Acute HIV Infection Decreases Exhausted/Activated CD4+ T Cells and CD8+ T Memory Stem Cells.

Several studies have identified main changes in T- and B-lymphocyte subsets during chronic HIV infection, but few data exist on how these subsets behave during the initial phase of HIV infection. We enrolled 22 HIV-infected patients during the acute stage of infection before the initiation of antiretroviral therapy (ART). Patients had blood samples drawn previous to ART initiation (T0), and at 2 (T1) and 12 (T2) months after ART initiation. We quantified cellular HIV-DNA content in sorted naïve and effector memory CD4 T cells and identified the main subsets of T- and B-lymphocytes using an 18-parameter flow cytometry panel. We identified correlations between the patients' clinical and immunological data using PCA. Effective HIV treatment reduces integrated HIV DNA in effector memory T cells after 12 months (T2) of ART. The main changes in CD4+ T cells occurred at T2, with a reduction of activated memory, cytolytic and activated/exhausted stem cell memory T (TSCM) cells. Changes were present among CD8+ T cells since T1, with a reduction of several activated subsets, including activated/exhausted TSCM. At T2 a reduction of plasmablasts and exhausted B cells was also observed. A negative correlation was found between the total CD4+ T-cell count and IgM-negative plasmablasts. In patients initiating ART immediately following acute/early HIV infection, the fine analysis of T- and B-cell subsets has allowed us to identify and follow main modifications due to effective treatment, and to identify significant changes in CD4+ and CD8+ T memory stem cells.

B cell subsets were associated with prognosis in elderly patients with community acquired pneumonia.

BACKGROUND: The role of B cell subsets remained to be elucidated in a variety of immune diseases, though which was used as an effective biomarker for anti-inflammatory or antiviral response. This study aimed to evaluate the early changes of B cell subtypes distribution in elderly patients with community acquired pneumonia (CAP), as well as the association between B cell subtypes and prognosis. METHODS: This prospective study included elderly patients with CAP, severe CAP (sCAP) and healthy elderly subjects between April 2016 and March 2018. Flow cytometry was used to detect CD3, CD20, HLA-DR, CD24, CD27, CD38, IgM, and IgD. CD20+ B cells were further divided into naïve B cells (Bn), IgM/D+ memory B cells (IgM+ Bm), switched B cells (SwB), and transitional B cells (Btr). RESULTS: A total of 22 healthy controls, 87 patients with CAP and 58 patients with sCAP were included in the study. Compared to CAP, sCAP was characterized by significantly lower absolute number of B cells, Bn and Btr, significantly lower Btr and Bn subset percentage, while percentage of IgM+ Bm was significantly higher. Heat map showed Bn and Btr on day 3 and day 7 was negatively correlated with activated partial prothrombin time (APTT), international normalized ratio (INR), sequential organ failure assessment score (SOFA) and Acute Physiology and Chronic Health Evaluation II (APACHE II). After 28-day follow-up, Btr percentage in survival group was significantly higher. Receiver operator characteristic (ROC) curve analysis found that Btr count showed sensitivity of 48.6% and specificity of 87.0% for predicting the 28-day survival, with an area under the ROC curves of 0.689 (p = 0.019). CONCLUSIONS: Severity and prognosis of CAP in elderly people is accompanied by changes in the B cell subsets. Btr subsets could play prognostic role for a short-term mortality of elderly CAP patients.

A combination of the percentages of IFN-γ+CD4+T cells and granzyme B+CD19+B cells is associated with acute hepatic rejection: a case control study.

BACKGROUND: T cells and B cells play a key role in alloimmune responses. We aimed to characterize the shift of T cell subsets and B cell subsets during acute hepatic rejection, and further determine whether they could serve as a prognostic marker. METHODS: Blood samples together with the clinical data from liver transplant recipients with and without acute hepatic rejection were collected and analyzed as well as from a validation cohort. RESULTS: Upon activation the expression of TGF-ß and granzyme B in CD19+B cells, and the expression of IL-2 and IFN-γ in CD4+T cells were higher in acute hepatic rejection. However, only the frequencies of granzyme B+CD19+B cells and IFN-γ+CD4+T cells correlated with liver function in addition to with each other. A combination of the two cell subsets as a novel marker could classify rejection versus non-rejection (area under the curve 0.811, p = 0.001) with the cut-off value of 62.93%, which was more sensitive for worse histological changes (p = 0.027). Moreover, the occurrence rate of acute rejection was higher in the group with the novel marker > 62.93% (p = 0.000). The role of the novel marker was further confirmed in a validation cohort, which was identified to be the only significant independent risk factor for acute rejection (odds ratio: 0.923; 95% CI confidence interval: 0.885-0.964; p = 0.000). CONCLUSIONS: A combination of the percentages of IFN-γ+CD4+T cells and granzyme B+CD19+B cells can distinguish rejection from non-rejection, which can be used as a potential prognostic marker for acute rejection in liver transplant recipients.

Characteristics of B lymphocyte infiltration in HPV+ head and neck squamous cell carcinoma.

Human papillomavirus (HPV) is an important etiological factor of head and neck squamous cell carcinoma (HNSCC). HPV+ HNSCC patients usually have a better prognosis, which probably results from the higher infiltration of B lymphocytes. This study was purposed to detect the infiltration of B lymphocyte subsets and the correlation between B lymphocyte subsets and the prognosis in HPV-related HNSCC. In this study, 124 HPV+ and 513 HPV- HNSCC samples were obtained from the Gene Expression Omnibus (GEO) database and The Cancer Genome Atlas (TCGA) database for transcriptomic analysis. Infiltration of B lymphocytes subsets was detected with 7 HPV+ HNSCC and 13 HPV- HNSCC tissues through immunohistochemistry and immunofluorescence. One HPV- HNSCC sample was detected with single-cell sequencing for chemokine analysis. In the results, the infiltration of plasma cells (CD19+ CD38+ ) and memory B cells (MS4A1+ CD27+ ) was higher in HPV+ HNSCC samples. High infiltration of plasma cells and memory B cells was related to a better prognosis. High density of B lymphocytes was positively correlated with high CXCL13 production mainly from CD4+ T lymphocytes in HNSCC. These results indicated that a high density of plasma cells and memory B cells could predict excellent prognosis. CD4+ T lymphocytes might affect B lymphocytes and their subsets through the CXCL13/CXCR5 axis in HNSCC.

Profiles of B-cell subsets in immunologically stable renal allograft recipients and end-stage renal disease patients.

BACKGROUND: Post-transplantation pharmacotherapies typically employ combinations of immunosuppressive agents that have been designed for targeted inhibition of T-cells and T-cell subsets. Studies of acute and chronic effects of clinically employed immunosuppressive agents on B-cells and B-cell subsets are significantly fewer in number and warrant further investigation. Accordingly, the goal of the present cross-sectional study is to functionally evaluate differences of B-cell subsets in patients with end-stage renal disease (ESRD) and immunologically stable renal transplant patients. PATIENTS AND METHODS: Of 103 patients who underwent renal transplantation, 73 patients were immunologically stable without rejection or infection. Among them, 34 patients were one-year post-transplantation, and 39 patients were five-year post-transplantation. The study also included 35 ESRD patients and 36 healthy volunteers. Flow cytometry identified B-cell subsets in the study groups. RESULTS: Renal allograft recipients had reduced percentages of total B-cells (CD19+) and regulatory B-cells (Breg) (CD38highCD27 + CD24+) compared with healthy controls. The percentage of transitional B-cells (IgM + CD38highCD24high) and marginal zone (MZ) B-cells (IgD-CD27+) was reduced in transplant recipients compared with patients with ESRD and healthy volunteers. The highest percentage of plasma cells (PCs) (CD38highCD27 + CD24-) was in patients with ESRD. In five-year post-transplantation group, CD38lowCD21- B-cells increased when compared with the other groups. Healthy volunteers and patients with ESRD had fewer unswitched memory (UM) B-cells (IgM + IgD + CD38lowCD27+), and increased isotype switched memory (ISM) B-cells (IgM-IgD-CD38lowCD27+). There was no difference in the percentage of naïve B-cells (IgD + CD27-) among diverse groups. CONCLUSIONS: The percentages of the total, transitional, Breg, PCs, MZ, and UM B-cell subsets in immunologically stable renal allograft recipients were significantly different from healthy controls. However, B-cell subsets in patients with ESRD were minimally different with immunologically stable renal allograft recipients.

Techniques to Study Antigen-Specific B Cell Responses.

Antibodies against foreign antigens are a critical component of the overall immune response and can facilitate pathogen clearance during a primary infection and also protect against subsequent infections. Dysregulation of the antibody response can lead to an autoimmune disease, malignancy, or enhanced infection. Since the experimental delineation of a distinct B cell lineage in 1965, various methods have been developed to understand antigen-specific B cell responses in the context of autoimmune diseases, primary immunodeficiencies, infection, and vaccination. In this review, we summarize the established techniques and discuss new and emerging technologies for probing the B cell response in vitro and in vivo by taking advantage of the specificity of B cell receptor (BCR)-associated and secreted antibodies. These include ELISPOT, flow cytometry, mass cytometry, and fluorescence microscopy to identify and/or isolate primary antigen-specific B cells. We also present our approach to identify rare antigen-specific B cells using magnetic enrichment followed by flow cytometry. Once these cells are isolated, in vitro proliferation assays and adoptive transfer experiments in mice can be used to further characterize antigen-specific B cell activation, function, and fate. Transgenic mouse models of B cells targeting model antigens and of B cell signaling have also significantly advanced our understanding of antigen-specific B cell responses in vivo.

B lymphocyte subsets and outcomes in patients with an initial diagnosis of transient hypogammaglobulinemia of infancy.

PURPOSE: Transient hypogammaglobulinemia of infancy (THI) is a common immunodeficiency, but definitive diagnosis can only be made retrospectively. While the pathogenesis is still unknown, abnormalities have been reported in the B cell compartment. In this study, we analysed the B cell subsets of patients with an initial THI diagnosis (n = 20) and compared them with those of healthy age-matched Turkish children (n = 72). METHODS: Flow cytometric analyses of the B subsets were performed by staining with anti-CD27-PE, anti-CD19-PerCP, anti-IgD-FITC and anti-IgM-APC antibodies. RESULTS: During a median follow-up of 6.6 years, 13 patients whose IgG levels had normalized before they reached four years of age were diagnosed with definitive THI. The memory subsets of these patients were lower but not statistically different from the healthy controls (HC). The remaining seven patients had prolonged hypogammaglobulinemia after the age of four and had significantly lower memory B cell subsets compared to the HC. On follow-up, these patients had not experienced recurrent infections or autoimmunity. Re-evaluation of patients' B cell subsets six years later showed that the memory B cell ratios had increased to levels comparable to HC, despite the patients still having mildly low IgG levels. CONCLUSION: Patients with prolonged hypogammaglobulinemia had lower levels of memory B cells despite having a similar clinical course to patients who had been diagnosed with definitive THI. This subgroup of putative THI patients poses a diagnostic and classification dilemma. Our results suggested that these patients' memory B cells and IgG levels may recover over time.

[B cells in head and neck oncology]. / B-Zellen in der Kopf-Hals-Onkologie.

As immunotherapy is becoming increasingly important in the treatment of head and neck cancer, a fundamental understanding of the immunological relationships in the tumor microenvironment is required. The importance of tumor-infiltrating B cells (TIL-B) has been largely neglected so far. In the current literature, however, a significant influence of B cells on tumor growth is described, so that this cell population is now also perceived as a therapeutic target structure. Regulatory B cells (Breg) represent a subset of B cells with immunosuppressive properties. In addition to the secretion of IL-10, Breg can be defined by their ability to produce adenosine. Adenosine is known as an immunosuppressive messenger in the tumor microenvironment whose effect can be prevented by immunotherapeutic approaches. Understanding the tumor immunological relationships, including the different B­cell functions, can help to effectively combine standard approaches including surgery or radiochemotherapy with immunotherapy. In the present article, recent findings on B cells and adenosine in head and neck cancer are described.

Changes in hematological indices and lymphocyte subsets in response to whole blood donation in healthy male donors.

Whole blood donation has immunomodulatory effects, and most of these have been observed at short intervals following blood donation. This study aimed to investigate the impact of whole blood donation on lymphocyte subsets over a typical inter-donation interval. Healthy male subjects were recruited to study changes in complete blood count (CBC) (n = 42) and lymphocyte subsets (n = 16) before and at four intervals up to 106 days following blood donation. Repeated measures ANOVA were used to compare quantitative variables between different visits. Following blood donation, changes in CBC and erythropoietin were as expected. The neutrophil count increased by 11.3% at 8 days (p < .001). Novel changes were observed in lymphocyte subsets as the CD4/CD8 ratio increased by 9.2% (p < .05) at 8 days and 13.7% (p < .05) at 22 days. CD16-56 cells decreased by 16.2% (p < .05) at 8 days. All the subsets had returned to baseline by 106 days. Regression analysis showed that the changes in CD16-56 cells and CD4/CD8 ratio were not significant (Wilk's lambda = 0.15 and 0.94, respectively) when adjusted for BMI. In conclusion, following whole blood donation, there are transient changes in lymphocyte subsets. The effect of BMI on lymphocyte subsets and the effect of this immunomodulation on the immune response merit further investigation.

Changes and significance of CD5+B lymphocyte in patients with systemic lupus erythematosus / 中华风湿病学杂志

Objective To measure the number of lymphocytes, B lymphocytes, CD5+B lymphocytes and level of IL-10 in peripheral blood of patients with systemic lupus erythematosus (SLE), and analyze their effects in the disease. Methods In this study, 84 cases of patients with SLE were randomly selected and evaluated according to the activity index (SLEDAI). These cases were divided into low activity group (SLEDAI0.05). In addition, the level of serum IL-10 in whether the low activity group (t=1.935, P=0.031) or the high activity group (t=3.048, P=0.012) was all higher than the normal control group. The level of serum IL-10 in patients with systemic lupus erythematosus was positively associated with SLEDAI score (r=0.425, P=0.024) and ESR (r=0.479, P=0.008), but was negatively correlated with complement 4 (r=-0.359, P=0.031). Conclusion The total number of lymphocytes in patients with SLE decreases significantly, while B lymphocytes increases significantly. The number of CD5+ B lymphocytes and the serum IL-10 level are also changed. It maybe related to the patient's inflammatory environment, and the number of CD5+B lymphocytes and the serum IL-10 level may be associated with disease activity.

CD19+ B cell subsets in the peripheral blood and skin lesions of psoriasis patients and their correlations with disease severity

T lymphocytes are important in the pathogenesis of psoriasis, and increasing evidence indicates that B cells also play an important role. The mechanisms of action, however, remain unclear. We evaluated the ratios of CD19+ B cells in peripheral blood mononuclear cells (PBMCs) from 157 patients with psoriasis (65 patients with psoriasis vulgaris, 32 patients with erythrodermic psoriasis, 30 patients with arthropathic psoriasis, and 30 patients with pustular psoriasis) and 35 healthy controls (HCs). Ratios of CD19+ B cells in skin lesions were compared with non-lesions in 7 erythrodermic psoriasis patients. The Psoriasis Area Severity Index (PASI) was used to measure disease severity. CD19+ B cell ratios in PBMCs from psoriasis vulgaris (at both the active and stationary stage) and arthropathic psoriasis patients were higher compared with HCs (P<0.01), but ratios were lower in erythrodermic and pustular psoriasis patients (P<0.01). CD19+ B cell ratios in erythrodermic psoriasis skin lesions were higher than in non-lesion areas (P<0.001). Different subsets of CD19+CD40+, CD19+CD44+, CD19+CD80+, CD19+CD86+, CD19+CD11b+, and CD19+HLA-DR+ B cells in PBMCs were observed in different psoriasis clinical subtypes. PASI scores were positively correlated with CD19+ B cell ratios in psoriasis vulgaris and arthropathic psoriasis cases (r=0.871 and r=0.692, respectively, P<0.01), but were negatively correlated in pustular psoriasis (r=-0.569, P<0.01). The results indicated that similar to T cells, B cells activation may also play important roles in different pathological stages of psoriasis.

B-cell-associated immune profiles in patients with decompensated cirrhosis.

OBJECTIVE: Previous observations on immune dysfunction in decompensated cirrhosis have raised the possibility of B-cell impairment. METHODS: B-cell subsets in decompensated cirrhotic patients were investigated. Twenty-six decompensated cirrhotic patients and 26 healthy controls were included in this study. The percentages of B-cell subsets, such as mature, memory, immature B cells, and interleukin (IL)-10+-B-cell subpopulations, were measured using fluorescent activated cell sorting. B-cell-associated cytokines (IL-10, IL-21 and IL-4) were determined using an enzyme-linked immunosorbent assay. RESULTS: The percentage of total B cells and mature B cells increased in patients with decompensated cirrhosis compared to healthy controls. The proportions of memory B cells were significantly lower in the decompensated cirrhosis group than the control group. However, the frequency of immature B cells and the percentage of IL-10-expressing cells that were CD19+, memory, mature, or immature B cells were not significantly different between the two groups. Serum levels of IL-10, IL-21, and IL-4 were significantly lower in the decompensated cirrhosis group compared to the control group. CONCLUSION: These results indicate significant alterations in peripheral blood B-cell subsets in patients with decompensated cirrhosis. Specifically, a profound reduction of memory B cells was observed in spite of an increase in total B-cell populations in decompensated cirrhotic patients. This implies the underlying mechanisms of impaired immune response in these patients.

Newly produced T and B lymphocytes and T-cell receptor repertoire diversity are reduced in peripheral blood of fingolimod-treated multiple sclerosis patients.

BACKGROUND: Fingolimod inhibits lymphocyte egress from lymphoid tissues, thus altering the composition of the peripheral lymphocyte pool of multiple sclerosis patients. OBJECTIVE: The objective of this paper is to evaluate whether fingolimod determines a decrease of newly produced T- and B-lymphocytes in the blood and a reduction in the T-cell receptor repertoire diversity that may affect immune surveillance. METHODS: Blood samples were obtained from multiple sclerosis patients before fingolimod therapy initiation and then after six and 12 months. Newly produced T and B lymphocytes were measured by quantifying T-cell receptor excision circles and K-deleting recombination excision circles by real-time PCR, while recent thymic emigrants, naive CD8(+) lymphocytes, immature and naive B cells were determined by immune phenotyping. T-cell receptor repertoire was analyzed by complementarity determining region 3 spectratyping. RESULTS: Newly produced T and B lymphocytes were significantly reduced in peripheral blood of fingolimod-treated patients. The decrease was particularly evident in the T-cell compartment. T-cell repertoire restrictions, already present before therapy, significantly increased after 12 months of treatment. CONCLUSIONS: These results do not have direct clinical implications but they may be useful for further understanding the mode of action of this immunotherapy for multiple sclerosis patients.

Changes of B lymphocyte subsets in peripheral blood of patients with rheumatoid arthritis and their ;significance / 中华微生物学和免疫学杂志

Objective To investigate the changes of B lymphocyte subsets ( naive B cells, memory B cells and plasmablasts) in peripheral blood of patients with rheumatoid arthritis ( RA) and their correla-tions with the clinical manifestation and laboratory indexes.Methods Sixty-six patients with RA were di-vided into two groups including the group with active RA and the group with inactive RA according to the dis-ease activity score in 28 Joints (DAS28).A control group with healthy subjects was set up accordingly.The distributions of B lymphocyte subsets in peripheral blood samples were detected with flow cytometry analysis and their correlations with clinical manifestations and laboratory indicators were analyzed.Results ( 1 ) Compared with healthy subjevts, the mean fluorescence intensities ( MFIs) of CD19 and the percentages of memory B cells in peripheral blood of the patients with RA were significantly decreased, while the percenta-ges of naive B cells were increased (P<0.05).The percentages of plasmablasts in the patients with active RA were significantly increased as compared with those of healthy subjects and the patients with inactive RA (P<0.05).(2) The percentages of plasmablasts in peripheral blood of the patients with RA were positively correlated with the joint tenderness count, joint swelling count and joint swelling index (P<0.05).(3) A positive correlation was found between the MFIs of CD19 and the erythrocyte sedimentation rates ( ESRs ) among the patients with RA.The percentages of plasmablasts were positively correlated with C reaction pro-tein (CRP) and anti-cyclic citrullinated peptide (anti-CCP) antibody (P<0.05).(4) The percentages of plasmablasts were also positively correlated with the DAS28 among the patients with RA ( R2=0.343, P<0.01).Conclusion The distributions of B lymphocyte subsets varied among the patients in different stages of RA, which were related to the patient′s clinical symptoms and laboratory indexes.The study suggested that different subsets of the B lymphocytes might play an important role in the pathological process of RA.

Regulatory B cells are numerically but not functionally deficient in anti-neutrophil cytoplasm antibody-associated vasculitis.

OBJECTIVES: B cells are central to the pathology of ANCA-associated vasculitis (AAV), a disease characterized by autoantibodies and effectively treated by rituximab. In addition to promoting inflammation, a subset of B cells act to suppress harmful autoimmune responses (Breg). The balance of effector and regulatory B cell subsets in AAV is not known. This study was conducted to assess the relative frequency of these subsets during different states of disease activity. METHODS: B memory (Bmem), naive (Bnaive) and regulatory (Breg) subsets were defined by their relative expression of CD24 and CD38. Function was assessed by cytokine production and suppressive action on CD4(+) Th1 activation evaluated in a co-culture system. RESULTS: Compared with healthy controls, the frequency of Breg (CD24(hi)CD38(hi)) was significantly reduced during disease remission in both proteinase 3 (PR3)- and MPO-ANCA patients and during acute disease in PR3-ANCA patients, while the frequency of memory cells (CD24(hi)CD38(lo)) was reduced during active disease and restored during remission. Breg cell frequency showed a positive correlation, while Bmem had an inverse correlation with IL-10 production in vitro. B and T cell co-cultures revealed that memory and naive B cell subsets augmented Th1 activation in vitro, which was prevented by Breg, and this pattern did not differ between remission AAV patients and controls. CONCLUSION: In remission there is a numerical, but not functional, deficiency in Breg and preservation of Bmem associated with reduced IL-10 production and increased Th1 activation in vitro. This imbalance may contribute to the high rate of relapse observed in AAV, especially in PR3-ANCA patients.

Circulating CD40+ and CD86+ B cell subsets demonstrate opposing associations with risk of stroke.

OBJECTIVE: Accumulating evidence shows that immune cells play an important role in atherosclerosis. Most attention has focused on the role of different T cell subsets, whereas the possible involvement of B cells has been less studied. In this study, we assessed the association of 2 different B cell subsets, CD19(+)CD40(+) and CD19(+)CD86(+) B cells, with risk for development of acute cardiovascular events. APPROACH AND RESULTS: The prospective study included 700 subjects randomly selected from the cardiovascular cohort of the Malmö Diet and Cancer study. Mononuclear leukocytes, stored at -140(○)C at the baseline investigation in 1991-1994, were thawed and B cell subsets analyzed by flow cytometry. Cytokine release from CD3/CD28-stimulated mononuclear leukocytes was measured with multiplex ELISA. Baseline carotid intima-media thickness and stenosis were assessed by ultrasonography, and clinical events were monitored through validated national registers during a median/mean follow-up time of 15 years. The subjects in the highest tertile of CD19(+)CD40(+) B cells had a significantly lower risk of incident stroke after adjustment for other risk factors. In contrast, CD19(+)CD86(+) B cells were associated with higher risk for development of a stroke event and increased release of proinflammatory cytokines from mononuclear leukocytes. CONCLUSIONS: These observations provide evidence for an involvement of B cells in the incidence of stroke and suggest that both pathogenic and protective B cell subsets exist.

Effects of tenghuanglin on injury to splenic lymphocyte induced by microwave radiation in rats / 解放军医学杂志

Objective To observe the effects of Tenghuanglin (THL) on injury to peripheral T and B lymphocytes induced by microwave radiation in rats, and explore the protective effects of THL against derangement of immunity in rat injury induced by microwave irradiation and its mechanism. Methods Eighty clean male SD rats were randomly divided into normal group (CON group), radiation group (RAD group), AduoLa Fuzhenglin (ADL) treatment group and THL treatment group, with 20 rats in each group. Before radiation, rats in ADL group and THL group were treated with ADL and THL respectively by gavage once per day for 7 days. Then, whole body of the rats was respectively exposed to 30 mW/cm2 microwave for 15 min. Rats in CON group were sham-radiated. The changes in splenic CD3+, CD4+, CD8+ T lymphocyte subsets and CD4SRA+ B lymphocyte subset were analyzed 7 and 14 days after radiation. Results Seven days after radiation, the splenic coefficient of RAD group was lower than that of CON group and THL group (P0.05). The CD4SRA+ B cell proportion of RAD group was lower than those of CON group and ADL group 7 days after radiation (P0.05). Conclusions The splenic T and B lymphocytes subsets decrease significantly at the early stage after microwave radiation in rats. Because of the rapid decrease in CD4+ T cell proportion, decreased CD4/CD8 ratio could lead to immune imbalance. Preventive treatment with THL could increase the T and B lymphocyte proportions and improve the CD4/CD8 ratio in rats after microwave radiation.