Lombard-Vadnais Félix, Chabot-Roy Geneviève, Zahn Astrid, Rodriguez Torres Sahily, Di Noia Javier M, Melichar Heather J, Lesage Sylvie
Immunologie-oncologie, Centre de recherche de l'Hôpital Maisonneuve-Rosemont, Montréal, QC H1T 2M4, Canada.
Department of Microbiology & Immunology, McGill University, Montreal, QC H3A 0G4, Canada.
iScience. 2022 Dec 21;26(1):105852. doi: 10.1016/j.isci.2022.105852. eCollection 2023 Jan 20.
Elimination of self-reactive T cells in the thymus is critical to establish T-cell tolerance. A growing body of evidence suggests a role for thymic B cells in the elimination of self-reactive thymocytes. To specifically address the role of thymic B cells in central tolerance, we investigated the phenotype of thymic B cells in various mouse strains, including non-obese diabetic (NOD) mice, a model of autoimmune diabetes. We noted that isotype switching of NOD thymic B cells is reduced as compared to other, autoimmune-resistant, mouse strains. To determine the impact of B cell isotype switching on thymocyte selection and tolerance, we generated NOD.AID mice. Diabetes incidence was enhanced in these mice. Moreover, we observed reduced clonal deletion and a resulting increase in self-reactive CD4 T cells in NOD.AID mice relative to NOD controls. Together, this study reveals that AID expression in thymic B cells contributes to T-cell tolerance.
胸腺中自身反应性T细胞的清除对于建立T细胞耐受性至关重要。越来越多的证据表明胸腺B细胞在清除自身反应性胸腺细胞中发挥作用。为了具体研究胸腺B细胞在中枢耐受中的作用，我们研究了各种小鼠品系（包括自身免疫性糖尿病模型非肥胖糖尿病（NOD）小鼠）中胸腺B细胞的表型。我们注意到，与其他自身免疫抗性小鼠品系相比，NOD胸腺B细胞的同种型转换减少。为了确定B细胞同种型转换对胸腺细胞选择和耐受性的影响，我们培育了NOD.AID小鼠。这些小鼠的糖尿病发病率增加。此外，相对于NOD对照，我们在NOD.AID小鼠中观察到克隆清除减少，从而导致自身反应性CD4 T细胞增加。总之，这项研究表明胸腺B细胞中AID的表达有助于T细胞耐受性。
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