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J Leukoc Biol. 2015 Mar;97(3):547-56. doi: 10.1189/jlb.3A0414-213RR. Epub 2014 Dec 16.

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

Author information

1
*Laboratory of Immunology, Institute of Basic Medical Sciences, Beijing, China; Department of Rheumatology, First Hospital of Jilin University, Changchun, China; Department of Immunology, Medical College of Henan University, Kaifeng, China; and State Key Laboratory of Toxicology and Medical Countermeasures, Beijing 100850, China.
2
*Laboratory of Immunology, Institute of Basic Medical Sciences, Beijing, China; Department of Rheumatology, First Hospital of Jilin University, Changchun, China; Department of Immunology, Medical College of Henan University, Kaifeng, China; and State Key Laboratory of Toxicology and Medical Countermeasures, Beijing 100850, China wang_renxi@yahoo.com liyan62033@gmail.com.

Abstract

This study tested the hypothesis that besides the spleen, LNs, peripheral blood, and thymus contain a regulatory IL-10-producing CD19(+)CD5(+)CD1d(high) 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 Cd19(Cre) (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(+)CD1d(hi) 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(+)CD1d(hi) 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(+)CD1d(hi)IL-10(+) Bregs play a critical role in the maintenance of immune homeostasis.

KEYWORDS:

CD72; Foxp3; regulatory T cells

PMID:
25516754
PMCID:
PMC5477891
DOI:
10.1189/jlb.3A0414-213RR
[Indexed for MEDLINE]
Free PMC Article

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