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.

中文翻译：

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SLE，反派分子或无辜旁观者中的自身反应性B细胞？

SLE（系统性红斑狼疮）中自身反应性B细胞发育的当前概念集中在外源性刺激和促使B细胞产生耐受性丧失的因素上。传统上，主要的耐受力丧失途径被认为受B细胞外因素的调节，包括B细胞受体（BCR）与树突状细胞，特别是浆细胞样树突状细胞（pDC）产生的同时I型干扰素（IFN）的自身抗原结合。后来，在自身反应性卵泡中，B细胞会遇到T滤泡辅助细胞（Tfh），产生白介素（IL）-21，IL-4和致病细胞因子IL-17和IFNγ（IFNɣ）。这篇综述讨论了这些机制，并着重指出了最近的进展，指出周边过渡性B细胞阶段是一个主要关头，在该阶段，通过发育B细胞引起的瞬时自分泌IFNβ表达对易分化为自身抗体的成浆细胞的外部因素具有更高的敏感性。最近的研究强调，过渡性B细胞异质性是通过塑造B细胞对细胞因子和其他环境因素的反应能力来确定内在抗性或对耐受性丧失的敏感性的决定因素。