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Discovery and Function of B-Cell IgD Low (BDL) B Cells in Immune Tolerance.

Abstract：

:It is now appreciated that in addition to their role in humoral immunity, B cells also exert regulatory mechanisms that lead to attenuation of inflammatory responses. The concept of B-cell regulation became well recognized when mice deficient in B cells due to genetic disruption were shown to be refractory to recovery from the signs of experimental autoimmune encephalomyelitis (EAE), the mouse model of multiple sclerosis. This seminal study spurred the search for B-cell regulatory phenotypes and mechanisms of action. Our approach was to utilize differential B-cell depletion with anti-CD20 to retain B cells whose presence were required to achieve EAE recovery. Utilizing flow cytometry, adoptive cell therapy and genetic approaches, we discovered a new B-cell subset that, upon adoptive transfer into B cell-deficient mice, was sufficient to promote EAE recovery. This B-cell subset is IgM+, but due to low/negative IgD cell surface expression, it was named B-cell IgD low (BDL). Mechanistically, we found that in the absence of BDL, the absolute cell number of CD4+Foxp3+ T regulatory cells (Treg), essential for immune tolerance, was significantly reduced. Furthermore, we found that BDL expression of glucocorticoid-induced tumor necrosis factor ligand (GITRL) was essential for induction of Treg proliferation and maintenance of their homeostasis. Thus, we have identified a new B-cell subset that is critical for immunological tolerance through interactions with Treg.

journal_name

J Mol Biol

journal_title

Journal of molecular biology

authors

Khalil MI,Gurski CJ,Dittel LJ,Neu SD,Dittel BN

doi

10.1016/j.jmb.2020.06.023

subject

Has Abstract

pub_date

2021-01-08 00:00:00

pages

166584

issue

1

eissn

0022-2836

issn

1089-8638

pii

S0022-2836(20)30428-9

journal_volume

433

pub_type

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