Sex differences characterize immune responses to viruses and autoimmune diseases like SLE. ABCs are an emerging population of CD11c+ T-bet+ B cells critical for antiviral responses and autoimmune disorders. DEF6 and SWAP70, are two homologous molecules whose combined absence in double-knock-out mice (DKOs) leads to a lupus syndrome in females marked by an accumulation of ABCs. Here we demonstrate that DKO ABCs exhibit sex-specific differences in their expansion, upregulation of an ISG signature, and further differentiation. BCR sequencing and fate mapping experiments reveal that DKO ABCs undergo oligoclonal expansion and differentiate into both CD11c+ and CD11c- effector populations with pathogenic and proinflammatory potential. Tlr7 duplication in DKO males overrides the sex-bias and further augments the dissemination and pathogenicity of ABCs resulting in severe pulmonary inflammation and early mortality. Thus, sexual dimorphism shapes the expansion, function, and differentiation of ABCs contributing to the sex-bias that accompanies TLR7-driven immunopathogenesis.

中文翻译：

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ABC功能和分化中的性别特异性差异标志着TLR7驱动的免疫发病机制

性别差异是对病毒和自身免疫性疾病（如SLE）的免疫反应的特征。ABC是新兴的CD11c + T-bet + B细胞，对抗病毒反应和自身免疫性疾病至关重要。DEF6和SWAP70是两个同源分子，它们在双重敲除小鼠（DKO）中的联合缺失会导致雌性狼疮综合征，其特征是ABC的积累。在这里，我们证明DKO ABC在其扩展，ISG签名的上调和进一步分化方面表现出性别特异性差异。BCR测序和命运定位实验表明，DKO ABC经历了寡克隆扩增，并分化为具有致病性和促炎性的CD11c +和CD11c-效应子群体。DKO雄性中的Tlr7重复覆盖了性别偏见，并进一步增加了ABC的传播和致病性，导致严重的肺部炎症和早期死亡。因此，性二态性影响着ABC的扩展，功能和分化，而ABC则促进了TLR7驱动的免疫发病机制伴随的性别偏见。