Dendritic Cells Regulate Extrafollicular Autoreactive B Cells Via T Cells Expressing Fas and Fas Ligand

Overview

Journal Immunity

Publisher Cell Press

Specialty Allergy & Immunology

Date 2016 Oct 30

PMID 27793595

Citations 17

Authors

Michelle L Ols

Jaime L Cullen

Adriana Turqueti-Neves

Josephine Giles

Mark J Shlomchik

Affiliations

Soon will be listed here.

Abstract

The extrafollicular (EF) plasmablast response to self-antigens that contain Toll-like receptor (TLR) ligands is prominent in murine lupus models and some bacterial infections, but the inhibitors and activators involved have not been fully delineated. Here, we used two conventional dendritic cell (cDC) depletion systems to investigate the role of cDCs on a classical TLR-dependent autoreactive EF response elicited in rheumatoid-factor B cells by DNA-containing immune complexes. Contrary to our hypothesis, cDC depletion amplified rather than dampened the EF response in Fas-intact but not Fas-deficient mice. Further, we demonstrated that cDC-dependent regulation requires Fas and Fas ligand (FasL) expression by T cells, but not Fas expression by B cells. Thus, cDCs activate FasL-expressing T cells that regulate Fas-expressing extrafollicular helper T (Tefh) cells. These studies reveal a regulatory role for cDCs in B cell plasmablast responses and provide a mechanistic explanation for the excess autoantibody production observed in Fas deficiency.

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