Critical role for thymic CD19+CD5+CD1dhiIL-10+ regulatory B cells in immune homeostasis

Abstract

This study tested the hypothesis that besides the spleen, LNs, peripheral blood, and thymus contain a regulatory IL-10-producing CD19+CD5+CD1dhigh B cell subset that may play a critical role in the maintenance of immune homeostasis. Indeed, this population was identified in the murine thymus, and furthermore, when cocultured with CD4+ T cells, this population of B cells supported the maintenance of CD4+Foxp3+ Tregs in vitro, in part, via the CD5–CD72 interaction. Mice homozygous for Cd19Cre (CD19−/−) express B cells with impaired signaling and humoral responses. Strikingly, CD19−/− mice produce fewer CD4+Foxp3+ Tregs and a greater percentage of CD4+CD8− and CD4−CD8+ T cells. Consistent with these results, transfer of thymic CD19+CD5+CD1dhi B cells into CD19−/− mice resulted in significantly up-regulated numbers of CD4+Foxp3+ Tregs with a concomitant reduction in CD4+CD8− and CD4−CD8+ T cell populations in the thymus, spleen, and LNs but not in the BM of recipient mice. In addition, thymic CD19+CD5+CD1dhi B cells significantly suppressed autoimmune responses in lupus-like mice via up-regulation of CD4+Foxp3+ Tregs and IL-10-producing Bregs. This study suggests that thymic CD19+CD5+CD1dhiIL-10+ Bregs play a critical role in the maintenance of immune homeostasis.