Novel Suppressive Function of Transitional 2 B Cells in Experimental Arthritis

Abstract

The immune system contains natural regulatory cells important in the maintenance of tolerance. Although this suppressive function is usually attributed to CD4 regulatory T cells, recent reports have revealed an immunoregulatory role for IL-10-producing B cells in the context of several autoimmune diseases including collagen-induced arthritis. In the present study, we attribute this suppressive function to a B cell subset expressing high levels of CD21, CD23, and IgM, previously identified as transitional 2-marginal zone precursor (T2-MZP) B cells. T2-MZP B cells are present in the spleens of naive mice and increase during the remission phase of arthritis. Following adoptive transfer to immunized DBA/1 mice, T2-MZP B cells significantly prevented new disease and ameliorated established disease. The suppressive effect on arthritis was paralleled by an inhibition of Ag-specific T cell activation and a reduction in cells exhibiting Th1-type functional responses. We also provide evidence that this regulatory subset mediates its suppression through the secretion of suppressive cytokines and not by cell-to-cell contact. The ability to regulate an established immune response by T2-MZP B cells endows this subset of B cells with a striking and previously unrecognized immunoregulatory potential.

IL-10-producing regulatory B cells (B10 cells) in autoimmune disease

“…The adoptive transfer of these B cells into DBA/1--T cell receptor--β-Tg mice, immunized with bovine collagen (type II collagen) emulsified in complete Freund's adjuvant, inhibits T H1 responses, prevents arthritis development, and is effective in ameliorating established disease. The adoptive transfer of CD21 hi CD23 + IgM + B cells from DBA/1 mice in the remission phase prevents CIA and reduces disease severity through IL-10 secretion [86]; a significant but less dramatic therapeutic effect on CIA progression is seen when cells from naïve mice are adoptively transferred. In addition, the adoptive transfer of ex vivo expanded CD1d hi CD5 + B cells in collagen-immunized mice delays arthritis onset and reduces disease severity, accompanied by a substantial reduction in the number of T H17 cells [61].…”

Retinoic acid-producing,ex-vivo-generated human tolerogenic dendritic cells induce the proliferation of immunosuppressive B lymphocytes

“…intermediate ) with at least one population of human Bregs recently reported and characterized [23,32,33]). Thus, we hypothesized that the increase in the frequency of B220 +…”

Immunologic Reconstitution After Rituximab in Systemic Lupus Erythematosus: Why Should We Care?

“…These results highlight an underappreciated point in the field that the therapeutic effect of B cell depletion therapy likely does not lie solely in the depletion of B cells but also in longterm reconstitution effects. Thus, although numerous examples of pathogenic roles for B cells have been provided by mouse models using either B cell-deficient mice or B cell depletion 12,13 , evidence is accumulating for regulatory B cells 14 capable of preventing or suppressing autoimmunity in different mouse models 15,16,17 . This protective role can be mediated by inducing T cell anergy during antigen presentation or inducing Treg expansion or activity 18 .…”