Mature IgDlow/- B cells maintain tolerance by promoting regulatory T cell homeostasis

Avijit Ray, Mohamed I. Khalil, Kirthi L. Pulakanti, Robert T. Burns, Cody J. Gurski, Sreemanti Basu, Demin Wang, Sridhar Rao and Bonnie N. Dittel ()
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Avijit Ray: Versiti Wisconsin
Mohamed I. Khalil: Versiti Wisconsin
Kirthi L. Pulakanti: Versiti Wisconsin
Robert T. Burns: Versiti Wisconsin
Cody J. Gurski: Versiti Wisconsin
Sreemanti Basu: Versiti Wisconsin
Demin Wang: Versiti Wisconsin
Sridhar Rao: Versiti Wisconsin
Bonnie N. Dittel: Versiti Wisconsin

Nature Communications, 2019, vol. 10, issue 1, 1-16

Abstract: Abstract A number of different B cell subsets have been shown to exhibit regulatory activity using a variety of mechanisms to attenuate inflammatory diseases. Here we show, using anti-CD20-mediated partial B cell depletion in mice, that a population of mature B cells distinguishable by IgDlow/- expression maintains tolerance by, at least in part, promoting CD4+Foxp3+ regulatory T cell homeostatic expansion via glucocorticoid-induced tumor necrosis factor receptor ligand, or GITRL. Cell surface phenotyping, transcriptome analysis and developmental study data show that B cells expressing IgD at a low level (BDL) are a novel population of mature B cells that emerge in the spleen from the transitional-2 stage paralleling the differentiation of follicular B cells. The cell surface phenotype and regulatory function of BDL are highly suggestive that they are a new B cell subset. Human splenic and peripheral blood IgDlow/- B cells also exhibit BDL regulatory activity, rendering them of therapeutic interest.

Date: 2019
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DOI: 10.1038/s41467-018-08122-9

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