Department of Immunology, Duke University Medical Center, Durham, NC 27710.
Departments of Pathology and Microbiology, University of Alabama at Birmingham, Birmingham, AL 35294.
J Immunol. 2013 Sep 1;191(5):2780-2795. doi: 10.4049/jimmunol.1300649. Epub 2013 Aug 5.
The spleen regulatory B cell subset with the functional capacity to express IL-10 (B10 cells) modulates both immune responses and autoimmune disease severity. However, the peritoneal cavity also contains relatively high frequencies of functionally defined IL-10-competent B10 cells. In this study, peritoneal cavity B10 cells shared similar cell surface phenotypes with their spleen counterparts. However, peritoneal cavity B10 cells were 10-fold more frequent among B cells than occurred within the spleen, intestinal tract, or mesenteric lymph nodes and were present at higher proportions among the phenotypically defined peritoneal B1a > B1b > B2 cell subpopulations. The development or localization of B10 cells within the peritoneal cavity was not dependent on the presence of commensal microbiota, T cells, IL-10 or B10 cell IL-10 production, or differences between their fetal liver or adult bone marrow progenitor cell origins. The BCR repertoire of peritoneal cavity B10 cells was diverse, as occurs in the spleen, and predominantly included germline-encoded VH and VL regions commonly found in either the conventional or B1 B cell compartments. Thereby, the capacity to produce IL-10 appears to be an intrinsic functional property acquired by clonally diverse B cells. Importantly, IL-10 production by peritoneal cavity B cells significantly reduced disease severity in spontaneous and induced models of colitis by regulating neutrophil infiltration, colitogenic CD4(+) T cell activation, and proinflammatory cytokine production during colitis onset. Thus, the numerically small B10 cell subset within the peritoneal cavity has regulatory function and is important for maintaining homeostasis within gastrointestinal tissues and the immune system.
具有表达 IL-10 功能能力的调节性 B 细胞亚群（B10 细胞）调节免疫反应和自身免疫性疾病的严重程度。然而，腹腔内也含有相对较高频率的具有功能定义的 IL-10 功能的 B10 细胞。在这项研究中，腹腔内 B10 细胞与脾脏对应物具有相似的细胞表面表型。然而，与脾脏、肠道或肠系膜淋巴结中的 B 细胞相比，腹腔内 B10 细胞的频率高出 10 倍，并且在表型定义的腹腔内 B1a>B1b>B2 细胞亚群中所占比例更高。B10 细胞在腹腔内的发育或定位不依赖于共生菌群、T 细胞、IL-10 或 B10 细胞的 IL-10 产生，也不依赖于其胎肝或成年骨髓祖细胞起源之间的差异。腹腔内 B10 细胞的 BCR 库是多样化的，就像在脾脏中一样，主要包括常见于常规或 B1 B 细胞区室的胚系编码 VH 和 VL 区域。因此，产生 IL-10 的能力似乎是克隆多样性 B 细胞获得的内在功能特性。重要的是，腹腔内 B 细胞产生的 IL-10 通过调节中性粒细胞浸润、结肠炎发病期间的 colitogenic CD4(+)T 细胞激活和促炎细胞因子产生，显著降低了自发性和诱导性结肠炎模型中的疾病严重程度。因此，腹腔内数量较少的 B10 细胞亚群具有调节功能，对于维持胃肠道组织和免疫系统的内稳态非常重要。
