Rubtsova Kira, Rubtsov Anatoly V, Thurman Joshua M, Mennona Johanna M, Kappler John W, Marrack Philippa
J Clin Invest. 2017 Apr 3;127(4):1392-1404. doi: 10.1172/JCI91250. Epub 2017 Feb 27.
B cells contribute to multiple aspects of autoimmune disorders and may play a role in triggering disease. Thus, targeting B cells may be a promising strategy for treating autoimmune disorders. Better understanding of the B cell subsets that are responsible for the development of autoimmunity will be critical for developing efficient therapies. Here we have reported that B cells expressing the transcription factor T-bet promote the rapid appearance of autoantibodies and germinal centers in spontaneous murine models of systemic lupus erythematosus (SLE). Conditional deletion of T-bet from B cells impaired the formation of germinal centers and mitigated the development of kidney damage and rapid mortality in SLE mice. B cell-specific deletion of T-bet was also associated with lower activation of both B cells and T cells. Taken together, our results suggest that targeting T-bet-expressing B cells may be a potential target for therapy for autoimmune diseases.
B细胞在自身免疫性疾病的多个方面发挥作用,可能在触发疾病中起作用。因此,靶向B细胞可能是治疗自身免疫性疾病的一种有前景的策略。更好地了解导致自身免疫发展的B细胞亚群对于开发有效的治疗方法至关重要。在这里,我们报道了在系统性红斑狼疮(SLE)的自发小鼠模型中,表达转录因子T-bet的B细胞促进自身抗体和生发中心的快速出现。从B细胞中条件性删除T-bet会损害生发中心的形成,并减轻SLE小鼠肾脏损伤的发展和快速死亡。B细胞特异性删除T-bet也与B细胞和T细胞的较低活化有关。综上所述,我们的结果表明,靶向表达T-bet的B细胞可能是自身免疫性疾病治疗的潜在靶点。