Autoantibodies in systemic autoimmune diseases: specificity and pathogenicity
Jolien Suurmond, Betty Diamond
Jolien Suurmond, Betty Diamond
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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 2

Proposed role of PRR activation and cross-reactivity in expansion of autoreactive B cells and their effector functions.

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Proposed role of PRR activation and cross-reactivity in expansion of aut...
(A) Self-antigens that bind PRRs can activate B cells. We hypothesize that the combined recognition of self-antigens by BCRs and PRRs is required for tolerance escape in autoreactive B cells. (B) B cells require recognition of antigen through their BCR for clonal expansion. As most autoantibodies recognize intracellular self-antigens, cross-reactivity to cell surface or extracellular molecules enhances clonal expansion and differentiation into memory and plasma cells.