Autoantibodies in systemic autoimmune diseases: specificity and pathogenicity
Jolien Suurmond, Betty Diamond
Jolien Suurmond, Betty Diamond
Published May 4, 2015
Citation Information: J Clin Invest. 2015;125(6):2194-2202. https://doi.org/10.1172/JCI78084.
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Review Series

Autoantibodies in systemic autoimmune diseases: specificity and pathogenicity

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.

Authors

Jolien Suurmond, Betty Diamond

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Figure 1

Mechanisms for autoantibody production: apoptosis, antigen modification, and cross-reactivity.

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Mechanisms for autoantibody production: apoptosis, antigen modification,...
Three models can explain the recognition of intracellular antigens by autoantibodies. (A) Cell death through apoptosis or necrosis leads to extracellular exposure of intracellular self-antigens through release of intracellular contents into the extracellular environment, formation of apoptosis blebs, or NETosis. If clearance mechanisms are insufficient, there may be recognition of these antigens by B cells and autoantibody production. (B) Modification of self-antigen generates neoantigens, to which B cells have not been tolerized. (C) Autoantibody production arises from responses to foreign antigens, which cross-react with self-antigens.