Low frequency of regulatory B-cells and increased CD4+ and CD8+ interferon-γ-producing cells in patients with tropical spastic paraparesis associated with human T-cell lymphotropic virus type

Abstract INTRODUCTION: Tropical spastic paraparesis/HTLV-1 associated myelopathy (TSP/HAM) is a disease caused by human T-cell lymphotropic virus type 1 (HTLV-I) that mainly infects CD4 T cells-for example, those of the CD4+CD25hiFOXP3+ [Treg] phenotype-where it inhibits forkhead box protein P3 (FOXP3) expression and promotes interferon-γ (IFN-γ) expression. However, the role it exerts on regulatory B cells (CD19+CD24hiCD38hi; Breg) is unknown. METHODS: The frequencies of Treg and Breg cells was evaluated and the Th1 profiles were assessed in TSP/HAM patients and healthy control subjects. RESULTS: Low percentages of Breg cells and high production of IFN-γ were observed in patients compared to those in healthy control subjects. CONCLUSIONS: The low percentage of Breg cells in patients and the increase in the frequency of Th1 cells suggest an imbalance in the control of the inflammatory response that contributes to the immunopathogenesis of TSP/HAM.

Toll-like receptor agonists Porphyromonas gingivalis LPS and CpG differentially regulate IL-10 competency and frequencies of mouse B10 cells

Abstract IL-10 expressing regulatory B cells (B10) play a key role in immune system balance by limiting excessive inflammatory responses. Effects of toll-like receptor signaling and co-stimulatory molecules on B10 activity during innate and adaptive immune responses are not fully understood. Objective This study is to determine the effects of P. gingivalis LPS and CpG on B10 cell expansion and IL-10 competency in vitro. Material and Methods Spleen B cells were isolated from C57BL/6J mice with or without formalin-fixed P. gingivalis immunization. B cells were cultured for 48 hours under the following conditions: CD40L, CD40L+LPS, CD40L+CpG, and CD40L+LPS+CpG in the presence or absence of fixed P. gingivalis. Percentages of CD1dhiCD5+ B cells were measured by flow cytometry. IL-10 mRNA expression and secreted IL-10 were measured by real-time quantitative PCR and by ELISA respectively. Results P. gingivalis LPS plus CD40L significantly increased CD1dhiCD5+ B cell percentages and secreted IL-10 levels in both immunized and non-immunized mice B cells in the presence or absence of P. gingivalis, compared with control group. Secreted IL-10 levels were significantly increased in CD40L+LPS treated group compared with CD40L treatment group in the absence of P. gingivalis. CpG plus CD40L significantly decreased CD1dhiCD5+ B cell percentages, but greatly elevated secreted IL-10 levels in immunized and non-immunized mice B cells in the absence of P. gingivalis, compared with CD40L treatment group. Conclusions P. gingivalis LPS and CpG differentially enhance IL-10 secretion and expansion of mouse B10 cells during innate and adaptive immune responses.

Regulatory B cells present in lymph nodes draining a murine tumor

In cancer, B cells have been classically associated with antibody secretion, antigen presentation and T cell activation. However, a possible role for B lymphocytes in impairing antitumor response and collaborating with tumor growth has been brought into focus. Recent reports have described the capacity of B cells to negatively affect immune responses in autoimmune diseases. The highly immunogenic mouse tumor MCC loses its immunogenicity and induces systemic immune suppression and tolerance as it grows. We have previously demonstrated that MCC growth induces a distinct and progressive increase in B cell number and proportion in the tumor draining lymph nodes (TDLN), as well as a less prominent increase in T regulatory cells. The aim of this research was to study B cell characteristics and function in the lymph node draining MCC tumor and to analyze whether these cells may be playing a role in suppressing antitumor response and favoring tumor progression. Results indicate that B cells from TDLN expressed increased CD86 and MHCII co-stimulatory molecules indicating activated phenotype, as well as intracellular IL-10, FASL and Granzyme B, molecules with regulatory immunosuppressive properties. Additionally, B cells showed high inhibitory upon T cell proliferation ex vivo, and a mild capacity to secrete antibodies. Our conclusion is that even when evidence of B cell-mediated activity of the immune response is present, B cells from TDLN exhibit regulatory phenotype and inhibitory activity, probably contributing to the state of immunological tolerance characteristic of the advanced tumor condition.