Deutsches Rheuma-Forschungszentrum, a Leibniz Institute, Charitéplatz 1, 10117 Berlin, Germany.
Department of EpiGenetics, Saarland University, Campus A2.4, Saarbrücken 66123, Germany.
Immunity. 2018 Jul 17;49(1):120-133.e9. doi: 10.1016/j.immuni.2018.06.007. Epub 2018 Jul 10.
B lymphocytes can suppress immunity through interleukin (IL)-10 production in infectious, autoimmune, and malignant diseases. Here, we have identified a natural plasma cell subset that distinctively expresses the inhibitory receptor LAG-3 and mediates this function in vivo. These plasma cells also express the inhibitory receptors CD200, PD-L1, and PD-L2. They develop from various B cell subsets in a B cell receptor (BCR)-dependent manner independently of microbiota in naive mice. After challenge they upregulate IL-10 expression via a Toll-like receptor-driven mechanism within hours and without proliferating. This function is associated with a unique transcriptome and epigenome, including the lowest amount of DNA methylation at the Il10 locus compared to other B cell subsets. Their augmented accumulation in naive mutant mice with increased BCR signaling correlates with the inhibition of memory T cell formation and vaccine efficacy after challenge. These natural regulatory plasma cells may be of broad relevance for disease intervention.
B 淋巴细胞可以通过产生白细胞介素 (IL)-10 来抑制感染、自身免疫和恶性疾病中的免疫。在这里，我们鉴定出了一种天然浆细胞亚群，该亚群特异性表达抑制性受体 LAG-3，并在体内介导此功能。这些浆细胞还表达抑制性受体 CD200、PD-L1 和 PD-L2。它们在无微生物群的情况下，通过 B 细胞受体 (BCR) 依赖性方式从各种 B 细胞亚群中发育而来。在受到挑战后，它们通过 Toll 样受体驱动的机制在数小时内上调 IL-10 的表达，而不增殖。该功能与独特的转录组和表观基因组相关联，与其他 B 细胞亚群相比，其 Il10 基因座的 DNA 甲基化程度最低。在 BCR 信号转导增加的幼稚突变小鼠中，这些天然调节性浆细胞的积累增加，与受到挑战后记忆 T 细胞形成和疫苗效力的抑制相关。这些天然调节性浆细胞可能对疾病干预具有广泛的相关性。
