Publication Date

2015

Journal Title

J Clin Invest

Abstract

In this Review we focus on the initiation of autoantibody production and autoantibody pathogenicity, with a special emphasis on the targeted antigens. Release of intracellular antigens due to excessive cell death or to ineffective clearance of apoptotic debris, modification of self-antigens during inflammatory responses, and molecular mimicry contribute to the initiation of autoantibody production. We hypothesize that those autoreactive B cells that survive and produce pathogenic autoantibodies have specificity for self-antigens that are TLR ligands. Such B cells experience both B cell receptor (BCR) activation and TLR engagement, leading to an escape from tolerance. Moreover, the autoantibodies they produce form immune complexes that can activate myeloid cells and thereby establish the proinflammatory milieu that further negates tolerance mechanisms of both B and T cells.

Volume Number

125

Issue Number

6

Pages

2194-2202

Document Type

Article

Status

Faculty, Northwell Researcher

Facility

School of Medicine; Northwell Health

Primary Department

Molecular Medicine

Additional Departments

General Internal Medicine

PMID

25938780

DOI

10.1172/jci78084


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