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

• DOI: 10.1189/jlb.3a0414-213rr
• Publication Date: 2014-12-17T05:42:54Z
• Authors: Chen Xing; Ning Ma; He Xiao; Xiaoqian Wang; Mingke Zheng; Gencheng Han; Guojiang Chen; Chunmei Hou; Beifen Shen; Yan Li; Renxi Wang
• Keywords: CD4-Positive T-Lymphocytes; 0301 basic medicine; B-Lymphocytes, Regulatory; Integrases; Immunity; Cell Differentiation; Forkhead Transcription Factors; Thymus Gland; CD8-Positive T-Lymphocytes; Lymphocyte Activation; Antibodies; Autoimmune Diseases; Interleukin-10; Up-Regulation; 3. Good health; Mice, Inbred C57BL; 03 medical and health sciences; Antigens, CD; Animals; Homeostasis; Cell Proliferation

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.