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

• Published in: Journal of leukocyte biology Vol. 97; no. 3; pp. 547 - 556
• Main Authors: Xing, Chen, Ma, Ning, Xiao, He, Wang, Xiaoqian, Zheng, Mingke, Han, Gencheng, Chen, Guojiang, Hou, Chunmei, Shen, Beifen, Li, Yan, Wang, Renxi
• Format: Journal Article
• Language: English
• Published: United States Society for Leukocyte Biology 01.03.2015
• Subjects: Animals; Antibodies - pharmacology; Antigens, CD - metabolism; Autoimmune Diseases - immunology; B-Lymphocytes, Regulatory - cytology; B-Lymphocytes, Regulatory - immunology; CD4-Positive T-Lymphocytes - cytology; CD4-Positive T-Lymphocytes - immunology; CD72; CD8-Positive T-Lymphocytes - cytology; CD8-Positive T-Lymphocytes - immunology; Cell Differentiation - immunology; Cell Proliferation; Forkhead Transcription Factors - metabolism; Foxp3; Homeostasis - immunology; Immunity; Inflammation, Extracellular Mediators, & Effector Molecules; Integrases - metabolism; Interleukin-10 - metabolism; Lymphocyte Activation - drug effects; Mice, Inbred C57BL; regulatory T cells; Thymus Gland - cytology; Up-Regulation; regulatory T cells; Foxp3; CD72
• ISSN: 0741-5400; 1938-3673
• DOI: 10.1189/jlb.3A0414-213RR

Thymic CD19+CD5+CD1dhiIL‐10+ B cells play a critical role in the maintenance of immune homeostasis. 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.