Regulatory B Cells: The New "It" Cell.
ABSTRACT Regulatory B cells (Breg) are a subpopulation of B cells that play a suppressive role in the immune system. The mechanism of how these immune cells perform their effects has been explored by experiments in mice and in humans. Intracellular staining for interleukin 10 continues to be a consistent and reproducible method of identifying Breg in mouse and human studies. The lack of Breg is associated with a worsening of several autoimmune diseases such as collagen-induced arthritis, systemic lupus erythematosus, and experimental autoimmune encephalomyelitis in murine studies. The purpose of this review is to provide a concise summary of the role of Breg in the immune system, including the most recently studied cell surface markers associated with Breg, and to describe the role of Breg in the etiology of several autoimmune diseases, the current understanding of Breg development, their role in the development of autoimmune diseases, and their role in inducing tolerance after transplantation.
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ABSTRACT: Bregs (regulatory B cells) are important in immune regulation. The regulatory factors on Breg functions are less understood. IGF2 (Insulin-like growth factor 2) is capable of inducing hematopoietic stem cell differentiation. This study aims to investigate the role of IGF2 in the development of Bregs and enhancement of Breg's function. In this study, the expression of IGF1R and IGF2R in OVAsBCs (ovalbumin (OVA)-specific B cells) was assessed by real time RT-PCR and Western blotting. The releasing of interleukin (IL)-10 from OVAsBCs and OVAsBC proliferation were assessed by enzyme-linked immunoassay and proliferation assay. The role of IGF2 in enhancing OVAsBCs' function was tested with an intestinal allergic inflammation mouse model. The results showed that OVAsBCs expressed high levels of IGF2R (IGF2 receptor). Exposure to both IGF2 and specific Ag (antigen), OVA, markedly enhanced the expression of IL-10 in OVAsBCs, as well as enhanced the IL-10+ OVAsBC proliferation. The concurrent exposure to IGF2 and specific Ag markedly induced the IL-10 promoter DNA demethylation via activating the STAT5 pathway. IGF2 also enhanced the OVAsBC proliferation in vivo and enhanced the effect of Ag-specific immunotherapy on inhibiting allergic inflammation in the intestine. We conclude that OVAsBCs express high levels of IGF2R. IGF2 increases the expression of IL-10 in OVAsBCs, enhances OVAsBC proliferation and the inhibitory effect on allergic inflammation.Journal of Biological Chemistry 05/2014; · 4.60 Impact Factor
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ABSTRACT: Gene replacement therapies, like organ and cell transplantation are likely to introduce neo-antigens that elicit rejection via humoral and/or effector T cell immune responses. Nonetheless, thanks to an ever growing body of pre-clinical studies it is now well accepted that gene transfer protocols can be specifically designed and optimized for induction of antigen-specific immune tolerance. One approach is to specifically express a gene in a tissue with a tolerogenic microenvironment such as the liver or thymus. Another strategy is to transfer a particular gene into hematopoietic stem cells or immunological precursor cells thus educating the immune system to recognize the therapeutic protein as "self". In addition, expression of the therapeutic protein in pro-tolerogenic antigen presenting cells such as immature dendritic cells and B cells has proven to be promising. All three approaches have successfully prevented unwanted immune responses in pre-clinical studies aimed at the treatment of inherited protein deficiencies, e.g. lysosomal storage disorders and hemophilia, and of type I diabetes and multiple sclerosis. In this review we focus on current gene transfer protocols that induce tolerance, including gene delivery vehicles and target tissues, and discuss successes and obstacles in different disease models.Molecular therapy. Methods & clinical development. 04/2014; 1:14013.
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ABSTRACT: A rare subset of IL-10-producing B cells, named regulatory B cells (Bregs) was recently identified in mice and humans. Currently, there are no unified cell surface markers to identify Bregs, and the relationship between the frequency of Bregs and HIV disease progression in chronic HIV infection is controversial. In this study, we determined whether the cell surface markers of Bregs reported for other diseases are suitable for identifying Bregs in HIV-infected patients. In addition, we examined the relationship between Bregs and HIV disease progression. We found that Breg frequency correlated positively with viral load and negatively with CD4 counts in chronic HIV infection. Following antiretroviral treatment, the CD4 counts increased and the frequency of Bregs decreased stepwise. There was no difference in IL-10 expression of CD1d(hi) or CD1d(lo) cells isolated from HIV infected patients. Therefore, CD1d may not be a marker of Bregs in HIV-infected patients.Microbiology and Immunology 06/2014; · 1.31 Impact Factor