Abstract
A number of different B cell subsets have been shown to exhibit regulatory activity using a variety of mechanisms to attenuate inflammatory diseases. Here we show, using anti-CD20-mediated partial B cell depletion in mice, that a population of mature B cells distinguishable by IgDlow/- expression maintains tolerance by, at least in part, promoting CD4+Foxp3+ regulatory T cell homeostatic expansion via glucocorticoid-induced tumor necrosis factor receptor ligand, or GITRL. Cell surface phenotyping, transcriptome analysis and developmental study data show that B cells expressing IgD at a low level (BDL) are a novel population of mature B cells that emerge in the spleen from the transitional-2 stage paralleling the differentiation of follicular B cells. The cell surface phenotype and regulatory function of BDL are highly suggestive that they are a new B cell subset. Human splenic and peripheral blood IgDlow/- B cells also exhibit BDL regulatory activity, rendering them of therapeutic interest.
Highlights
A number of different B cell subsets have been shown to exhibit regulatory activity using a variety of mechanisms to attenuate inflammatory diseases
We found that the ability of B cells to homeostatically expand T regulatory cells (Tregs) was glucocorticoid-induced tumor necrosis factor receptor ligand (GITRL)-dependent, but IL-10independent[3]
Total B cell depletion with anti-CD20 immunoglobulin G 2a (IgG2a) prior to EAE induction led to significantly reduced Treg numbers and the inability to recover from EAE3, indicating that the protective B cell population was depleted
Summary
A number of different B cell subsets have been shown to exhibit regulatory activity using a variety of mechanisms to attenuate inflammatory diseases. These authors contributed : Avijit Ray, A regulatory role for B cells in controlling the severity of autoimmunity was first described by us in the mouse model of multiple sclerosis (MS), experimental autoimmune encephalomyelitis (EAE)[1]. B10.PL mice deficient in B cells (μMT) immunized with the myelin basic protein (MBP)-immunodominant peptide Ac1–11 were unable to recover from the signs of EAE exhibiting a chronic disease course[1]. We subsequently reproduced these findings in mice on the B10.PL background using adoptive transfer EAE and in anti-CD20-depleted mice[2,3].
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