CNRS UPR 3572 "Immunopathology and Therapeutic Chemistry"/Laboratory of Excellence Médalis, Institute of Molecular and Cellular Biology (IBMC), Strasbourg, France.
Department of Clinical Immunology and Internal Medicine, National Reference Center for Autoimmune Diseases, Hôpitaux Universitaires de Strasbourg, Strasbourg, France.
Sci Rep. 2017 Oct 16;7(1):13232. doi: 10.1038/s41598-017-13422-z.
The phenotypic characterization of self-reactive B cells producing autoantibodies is one of the challenges to get further insight in the physiopathology of autoimmune diseases. We took advantage of our previously developed flow cytometry method, using labeled nucleosomes, prominent autoantigens in systemic lupus erythematosus, to analyze the phenotype of self-reactive B cells in the anti-DNA B6.56R mouse model. We showed that splenic anti-nucleosome B cells express mostly kappa light chains and harbor a marginal zone phenotype. Moreover, these autoreactive B cells fail to acquire a germinal center phenotype and are less abundant in the transitional T3 compartment. In conclusion, the direct detection of autoreactive B cells helped determine their phenotypic characteristics and provided a more direct insight into the B cell tolerance process in B6.56R mice. This method constitutes an interesting new tool to study the mechanisms of B cell tolerance breakdown in B6.56R mice crossed with autoimmune prone models.
自身反应性 B 细胞产生自身抗体的表型特征是深入了解自身免疫性疾病病理生理学的挑战之一。我们利用之前开发的使用标记核小体的流式细胞术方法，核小体是系统性红斑狼疮中的主要自身抗原，来分析抗 DNA B6.56R 小鼠模型中的自身反应性 B 细胞的表型。我们表明，脾脏抗核小体 B 细胞主要表达 κ 轻链，并具有边缘区表型。此外，这些自身反应性 B 细胞未能获得生发中心表型，在过渡 T3 区的丰度较低。总之，自身反应性 B 细胞的直接检测有助于确定其表型特征，并更直接地了解 B6.56R 小鼠中的 B 细胞耐受过程。该方法构成了一种有趣的新工具，可用于研究与自身免疫倾向模型杂交的 B6.56R 小鼠中 B 细胞耐受破坏的机制。
