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Autoreactive B cells in SLE, villains or innocent bystanders?
Author(s) -
Hamilton Jennie A.,
Hsu HuiChen,
Mountz John D.
Publication year - 2019
Publication title -
immunological reviews
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.839
H-Index - 223
eISSN - 1600-065X
pISSN - 0105-2896
DOI - 10.1111/imr.12815
Subject(s) - immunology , biology , peripheral tolerance , b cell , autocrine signalling , autoantibody , autoimmunity , microbiology and biotechnology , receptor , immune system , antibody , genetics
The current concepts for development of autoreactive B cells in SLE (systemic lupus erythematosus) focus on extrinsic stimuli and factors that provoke B cells into tolerance loss. Traditionally, major tolerance loss pathways are thought to be regulated by factors outside the B cell including autoantigen engagement of the B‐cell receptor (BCR) with simultaneous type I interferon (IFN) produced by dendritic cells, especially plasmacytoid dendritic cells (pDCs). Later, in autoreactive follicles, B‐cells encounter T‐follicular helper cells (Tfh) that produce interleukin (IL)‐21, IL‐4 and pathogenic cytokines, IL‐17 and IFN gamma (IFNɣ). This review discusses these mechanisms and also highlights recent advances pointing to the peripheral transitional B‐cell stage as a major juncture where transient autocrine IFNβ expression by developing B‐cells imprints a heightened susceptibility to external factors favoring differentiation into autoantibody‐producing plasmablasts. Recent studies highlight transitional B‐cell heterogeneity as a determinant of intrinsic resistance or susceptibility to tolerance loss through the shaping of B‐cell responsiveness to cytokines and other environment factors.