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2.
Clin Exp Immunol ; 124(2): 172-9, 2001 May.
Article in English | MEDLINE | ID: mdl-11422192

ABSTRACT

Although most chemotherapeutic agents are known to cause primarily reduction or suppression of immune responses, surprisingly little is known about the influence of cytostatic agents on lymphoid tissue compartments such as the splenic marginal zone. The marginal zone plays an important role in the defence against encapsulated bacteria, which are potential candidates for postchemotherapeutic infections. We studied the effect of three different cytostatic agents (cisplatin, methotrexate, and cyclophosphamide) on B cell subpopulations in a rat model. Rats received a single dose of a single cytostatic agent and were sacrificed at different time points after treatment. Bone marrow, blood, mesenteric lymph nodes and spleens were analysed by flow-cytometry and immunohistochemistry. All three cytostatic agents showed severe bone marrow depression. CP and MTX showed only mild reduction of cell populations in the spleen. CyPh showed a severe reduction of recirculating follicular B (RF-B) cells and marginal zone B (MZ-B) cells. At day 24 most populations were already recovered, but RF-B cells and MZ-B cells were still reduced. The reduction of the marginal zone and late recovery may imply that, beside the overall increased infection risk due to neutropenia, patients treated with chemotherapy are at risk for developing infections from encapsulated bacteria for a considerable period of time after treatment, extending beyond the period of bone marrow depression.


Subject(s)
Antibody Formation/drug effects , Antineoplastic Agents/toxicity , B-Lymphocytes/drug effects , Bone Marrow Cells/drug effects , Spleen/drug effects , Animals , B-Lymphocytes/cytology , Blood Cells/cytology , Blood Cells/drug effects , Bone Marrow Cells/cytology , Cisplatin/toxicity , Cyclophosphamide/toxicity , Lymph Nodes/cytology , Lymph Nodes/drug effects , Male , Mesentery/cytology , Mesentery/drug effects , Methotrexate/toxicity , Rats , Rats, Wistar , Spleen/cytology
3.
Immunology ; 103(2): 199-209, 2001 Jun.
Article in English | MEDLINE | ID: mdl-11412307

ABSTRACT

Brown-Norway (BN) and Dorus Zadel Black (DZB) rats develop a T-cell-dependent membranous glomerulopathy (MGP) with high proteinuria and antiglomerular basement membrane (GBM) autoreactive antibodies (Abs), upon exposure to mercuric chloride (HgCl2). Laminin is an important autoantigenic target of the anti-GBM Abs, absorbing approximately 30% of the anti-GBM reactivity. Although many anti-GBM Abs have undergone isotype switching, it is currently unclear whether affinity maturation occurs during the HgCl2-induced autoimmune response. To address this question we analysed the rearranged immunoglobulin heavy chain variable-region genes (VHDJH regions) of 15 mAbs that were previously obtained from HgCl2-treated rats. Seven of these mAbs exhibit reactivity towards laminin. Our study showed that the VH-gene usage of antilaminin mAbs is largely restricted to the PC7183 VH-gene family (six out of seven). In addition, we demonstrated that at least three out of six laminin reactive and five out of six non-laminin-binding mAbs are encoded by germline VH genes (a total of eight out of 12 mAbs). Of the eight mAbs that are encoded by germline VH genes, seven are of a non-immunoglobulin M (IgM) isotype, indicating that isotype switching has occurred in these mAbs in the absence of somatic mutations. The mutations observed in the VH genes of the four remaining mAbs do not provide strong evidence for antigenic selection. The data support the notion that B cells in this model of MGP are not subjected to affinity maturation and probably result from polyclonal B-cell activation.


Subject(s)
Autoantibodies/biosynthesis , Autoimmune Diseases/immunology , Genes, Immunoglobulin/immunology , Glomerulonephritis, Membranous/immunology , Amino Acid Sequence , Animals , Antibodies, Monoclonal/immunology , Autoimmune Diseases/chemically induced , Autoimmune Diseases/genetics , Autoimmunity , Base Sequence , Complementarity Determining Regions/genetics , DNA, Complementary/genetics , Genes, Immunoglobulin/genetics , Glomerulonephritis, Membranous/chemically induced , Glomerulonephritis, Membranous/genetics , Immunoglobulin Class Switching , Laminin/immunology , Mercuric Chloride , Molecular Sequence Data , Rats , Rats, Inbred BN
4.
Tissue Antigens ; 58(4): 234-42, 2001 Oct.
Article in English | MEDLINE | ID: mdl-11782274

ABSTRACT

The splenic marginal zone of adult humans contains B cells, of which most express CD27, an antigen only recently identified as a marker for somatically mutated memory B cells. We investigated whether and to which extent the developing marginal zone in infants and children is populated by either memory (CD27+) or naive (CD27-) B cells. Frozen sections of 32 spleens of infants and children ranging in age from 6 days to 15 years and 6 adult spleens were investigated. The expression of CD27 in combination with monoclonal antibodies against CD3, CD21, IgM, IgD and ASM-1 was analyzed by immunohistochemistry. The marginal zone was already present at 4 months after birth but CD21 expression was observed first after 2 years. CD27-positive marginal zone B cells were observed firstly 2 years after birth and increased in number to adult levels at the age of 5 years. We demonstrated that the MZ of infants and young children is populated by naive B cells, which are replaced by memory B cells in a time frame of 2 to 5 years. Before the age of 2 years, although present, memory B cells appear to be unable to colonize the marginal zone. Because of the absence of memory B cells in the marginal zone, the immune system of a child is not capable to initiate a rapid secondary humoral immune response comparable to the adult immune response.


Subject(s)
B-Lymphocytes/cytology , B-Lymphocytes/immunology , Receptors, Complement 3d/analysis , Spleen/cytology , Spleen/immunology , Tumor Necrosis Factor Receptor Superfamily, Member 7/analysis , Adolescent , Adult , Child, Preschool , Gene Expression , Humans , Immunologic Memory , Infant , Infant, Newborn , Lymphocyte Subsets/immunology
6.
J Immunol ; 165(11): 6156-69, 2000 Dec 01.
Article in English | MEDLINE | ID: mdl-11086049

ABSTRACT

The present study was performed to analyze whether marginal zone B (MZ-B) cells in nondeliberately immunized adult rats are selected on basis of the specificity of their B cell receptor, and to determine to what extent memory B cells contribute to the MZ-B cell subset. To this end, the Ig PC7183 V(H) gene repertoire was studied among V(H)DJ(H)-mu transcripts expressed in four sequential stages of B cell development, of two individual untreated adult rats. B cell subsets, i.e., pro/pre-B cells and newly formed B (NF-B) cells from bone marrow, and recirculating follicular B cells and MZ-B cells from spleen were sorted by flow cytometry. In addition, from one these rats, cells were microdissected from follicular and MZ areas of the spleen and productive PC7183 V(H) gene rearrangements were analyzed for the presence of somatic mutations. Sequence analysis reveals that most MZ-B cells in the adult rat, either defined by flow cytometry or by their anatomical location in the spleen, express germline encoded V(H) genes (naive MZ-B cells) and a minor fraction (about 20%) of the MZ-B cells carry somatic mutations (memory MZ-B cells). In addition, we show that naive MZ-B cells are a selected population of cells, both based on PC7183 V(H) gene repertoire and on the length of the Ig heavy (H) chain complementarity-determining region 3 (H-CDR3) region, i.e., PC7183 V(H)DJ(H)-mu transcripts of MZ-B cells carry significantly shorter H-CDR3 regions than other B cell subsets.


Subject(s)
B-Lymphocyte Subsets/immunology , B-Lymphocyte Subsets/metabolism , Bone Marrow Cells , Immunoglobulin Heavy Chains/genetics , Immunoglobulin Variable Region/genetics , Spleen/cytology , Amino Acid Sequence , Animals , Antibody Diversity/genetics , Base Sequence , Bone Marrow Cells/immunology , Bone Marrow Cells/metabolism , Cell Separation , Complementarity Determining Regions/biosynthesis , Complementarity Determining Regions/genetics , DNA Mutational Analysis , Dissection , Flow Cytometry , Gene Expression Regulation/immunology , Gene Rearrangement, B-Lymphocyte, Heavy Chain , Germ-Line Mutation , Immunoglobulin Heavy Chains/biosynthesis , Immunoglobulin J-Chains/biosynthesis , Immunoglobulin J-Chains/genetics , Immunoglobulin Variable Region/biosynthesis , Immunoglobulin mu-Chains/biosynthesis , Immunoglobulin mu-Chains/genetics , Ligands , Male , Micromanipulation , Molecular Sequence Data , Multigene Family/immunology , Rats , Rats, Inbred Strains , Reverse Transcriptase Polymerase Chain Reaction , Spleen/immunology , Spleen/metabolism , Transcription, Genetic/immunology
7.
Eur J Immunol ; 29(5): 1522-31, 1999 05.
Article in English | MEDLINE | ID: mdl-10359106

ABSTRACT

The marginal zone is a unique compartment that is only found in the spleen. Rat marginal zone B cells (MZ-B) can be distinguished from other B cells, e.g. recirculating follicular B cells (RF-B), by several phenotypic characteristics. Typically MZ-B cells are surface (s)IgMhi, sIgDlo and CD45R(B220)lo, whereas RF-B cells are sIgMlo, sIgDhi and CD45Rhi. In addition, MZ-B cells stain strongly with HIS57, a newly developed monoclonal antibody. The developmental pathway and origin of MZ-B cells are not exactly known. However, previous studies indicate that recirculating (i. e. thoracic duct) B cells can give rise to MZ-B cells. Here the origin of (naive) MZ-B cells was studied using adriamycin (doxorubicin)-induced B cell depletion. Using three-color flow cytometry and immunohistology we show that 2 days after a single i.v. injection of the anti-tumor drug adriamycin only RF-B cells can be detected, while all other B cell subpopulations are depleted, including all bone marrow precursor B cells. By studying the sequential reappearance of various B cell subsets and their precursors after adriamycin administration we show that MZ-B cells and the splenic marginal zone can be detected at a time point at which newly generated B cells (immature B cells) are not yet present. Given the observation that only RF-B cells were present at this time, we conclude that RF-B cells are the immediate MZ-B precursor cells.


Subject(s)
B-Lymphocytes/cytology , Animals , B-Lymphocyte Subsets/immunology , B-Lymphocytes/classification , B-Lymphocytes/immunology , Cell Differentiation , Doxorubicin , Flow Cytometry , Lymphocytes , Male , Mice , NF-kappa B/metabolism , Rats , Spleen/cytology
8.
Dev Immunol ; 6(1-2): 81-7, 1998.
Article in English | MEDLINE | ID: mdl-9716908

ABSTRACT

Next to conventional B cells (or B-2 cells), peritoneal B-1 cells have been shown to contribute significantly to the production of IgA-secreting plasma cells in the gut. Evidence for this was mainly based on studies comprising manipulated animals, including lethally X-irradiated and transgenic mice. To examine the ability of peritoneal B-1 cells from untreated mice to switch actively to IgA in vivo, we performed RT-PCR analysis on FACS-sorted peritoneal B-cell subsets from untreated BALB/c mice in order to examine the presence of germline C alpha mRNA and mature C alpha mRNA transcripts. Germline C alpha and mature C alpha transcripts were readily detectable in peritoneal B-1 cells (defined as IgMbright/IgDdull), but not, or very little, in peritoneal B-2 cells (defined as IgMdull/IgDbright). Moreover, by subdividing the B-1-cell population in CD5+ B-1a cells and CD5- B-1b cells, it was shown that in vivo expression of germline C alpha and mature C alpha transcripts was largely restricted to the B-1b-cell lineage. These results indicate that peritoneal B-1 cells indeed are capable to switch to IgA under normal physiological conditions and hereby further support the view that B-1 cells contribute significantly to the mucosal IgA response, albeit this function appears to be restricted to the B-1b-cell subset.


Subject(s)
B-Lymphocytes/metabolism , Immunoglobulin A/genetics , Peritoneal Cavity/cytology , RNA, Messenger/analysis , Animals , Female , Male , Mice , Mice, Inbred BALB C , Rats
11.
J Behav Med ; 17(5): 459-77, 1994 Oct.
Article in English | MEDLINE | ID: mdl-7877156

ABSTRACT

Forty-one subjects diagnosed with systemic lupus erythematosus (SLE) were recruited from across the United States. Regressions were conducted to evaluate the relation among stress, depression, anxiety, anger, and SLE symptom complaints. Negative weighting of major life events predicted symptom history. Significant hierarchical regressions using negative weighting of major life events, impact of daily stress, depression, anxiety, and anger were found for severity of joint pain, abdominal distress, and rash. Analyses using 1-day-lagged predictors yielded similar results. Within-subject analyses suggested that there was much individual variability in the strength of the stress-illness relation. Thus, some individuals appeared to be stress responders, while others did not. Findings for impact of minor life events and depression were consistent across the different levels of analyses. It was concluded that stress, depression, anxiety, and anger are associated with, and may exacerbate, self-reported symptomatology of SLE patients.


Subject(s)
Anxiety/psychology , Depression/psychology , Lupus Erythematosus, Systemic/psychology , Stress, Psychological/physiopathology , Adult , Anger , Causality , Female , Humans , Life Change Events , Lupus Erythematosus, Systemic/physiopathology , Male , Prospective Studies , Regression Analysis , Stress, Psychological/psychology , Surveys and Questionnaires
12.
South Med J ; 83(9): 1016-8, 1990 Sep.
Article in English | MEDLINE | ID: mdl-2402642

ABSTRACT

Data from questionnaires completed by 419 10th-grade girls were analyzed as part of a school health education program. The questionnaire was designed to collect knowledge of, attitudes toward, and experiences with cancer and cancer prevention. Data were collected from randomly selected health classes preceding a presentation on breast and cervical cancer prevention. Results showed that the girls were pessimistic about chances of surviving cancer and did not differentiate survival by type or site of the cancer. Although there was considerable confusion about its purpose, 27.6% reported having had a Papanicolaou smear within the past year and 79.2% correctly identified the Pap smear as a test for cancer.


Subject(s)
Papanicolaou Test , Uterine Cervical Neoplasms/prevention & control , Vaginal Smears , Adolescent , Female , Health Education , Health Knowledge, Attitudes, Practice , Humans , North Carolina , Surveys and Questionnaires
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