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


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.

SUBMITTER: Ray A 

PROVIDER: S-EPMC6331566 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

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Mature IgD<sup>low/-</sup> B cells maintain tolerance by promoting regulatory T cell homeostasis.

Ray Avijit A   Khalil Mohamed I MI   Pulakanti Kirthi L KL   Burns Robert T RT   Gurski Cody J CJ   Basu Sreemanti S   Wang Demin D   Rao Sridhar S   Dittel Bonnie N BN  

Nature communications 20190114 1


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 IgD<sup>low/-</sup> expression maintains tolerance by, at least in part, promoting CD4<sup>+</sup>Foxp3<sup>+</sup> regulatory T cell homeostatic expansion via glucocorticoid-induced tumor necrosis factor receptor ligand,  ...[more]

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