Regulatory B Cells (B10 Cells) Have a Suppressive Role in Murine Lupus: CD19 and B10 Cell Deficiency Exacerbates Systemic Autoimmunity

Abstract

B cells play critical roles in the pathogenesis of lupus. To examine the influence of B cells on disease pathogenesis in a murine lupus model, New Zealand Black and New Zealand White F1 hybrid (NZB/W) mice were generated that were deficient for CD19 (CD19−/− NZB/W mice), a B cell-specific cell surface molecule that is essential for optimal B cell signal transduction. The emergence of anti-nuclear antibodies was significantly delayed in CD19−/− NZB/W mice in comparison with wild type NZB/W mice. However, the pathologic manifestations of nephritis appeared significantly earlier and survival was significantly reduced in CD19−/− NZB/W mice in comparison with wild type mice. These results demonstrate both disease promoting and protective roles for B cells in lupus pathogenesis. Recent studies have identified a potent regulatory B cell subset (B10 cells) within the rare CD1dhiCD5+ B cell subset of the spleen that regulates acute inflammation and autoimmunity through the production of IL-10. In wild type NZB/W mice, the CD1dhiCD5+B220+ B cell subset that includes B10 cells was increased by 2.5-fold during the disease course, while CD19−/− NZB/W mice lacked this CD1dhiCD5+ regulatory B cell subset. However, the transfer of splenic CD1dhiCD5+ B cells from wild type NZB/W mice into CD19−/− NZB/W recipients significantly prolonged their survival. Furthermore, regulatory T cells were significantly decreased in CD19−/− NZB/W mice, but the transfer of wild type CD1dhiCD5+ B cells induced Treg cell expansion in CD19−/− NZB/W mice. These results demonstrate an important protective role for regulatory B10 cells in this systemic autoimmune disease.

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

“…B10 cells are phenotypically similar in NZB/W F1 and C57BL/6 mice, but are expanded significantly in young NZB/W F1 mice [87]. In wildtype NZB/W mice, the CD1d hi CD5 + B220 + B cell subset, which is enriched in B10 cells, is increased 2.5-fold during the disease course, whereas CD19 --/-- NZB/W mice lack this CD1d hi CD5 + regulatory B cell subset [88]. Finally, the potential therapeutic effect of B10 cells in lupus is highlighted by the prolonged survival of CD19 --/-- NZB/W recipients following the adoptive transfer of splenic CD1d hi CD5 + B cells from wildtype NZB/W mice [88].…”

“…In wildtype NZB/W mice, the CD1d hi CD5 + B220 + B cell subset, which is enriched in B10 cells, is increased 2.5-fold during the disease course, whereas CD19 --/-- NZB/W mice lack this CD1d hi CD5 + regulatory B cell subset [88]. Finally, the potential therapeutic effect of B10 cells in lupus is highlighted by the prolonged survival of CD19 --/-- NZB/W recipients following the adoptive transfer of splenic CD1d hi CD5 + B cells from wildtype NZB/W mice [88]. Studies in the NZB/W spontaneous lupus model therefore suggest that B10 cells have protective and potentially therapeutic effects.…”

Regulatory B Cells - Implications in Autoimmune and Allergic Disorders

“…Although, auto-antibody accumulation was significantly delayed in these mice, nephritis appeared earlier and survival was reduced compared to wild type NZB/W mice. Adoptive transfer of wild type CD1d hi CD5 + splenic B cells containing IL-10 producing regulatory B cells into CD19 deficient recipients significantly prolonged survival (Watanabe, Ishiura et al 2010). Adoptive transfer of in vitro anti-CD40 stimulated T2 B cells into lupus-prone mice also improved renal disease and survival by an IL-10-dependent mechanism.…”

Regulatory B Cells and Allergy: Uncovering the Link

“…We describe the types and mechanisms of action of B cells and their role in the pathogenesis of several allergic diseases (allergic 205 [72], EAE [73], lupus [74], EAMG [75], collagen-induced arthritis [76], colitis [77], allergic airway inflammation [21,24] …”