Translational Cell Genetics, Department of Pharmacology and Genetics, Medical University of Innsbruck, Innsbruck, Austria.
Institute for Biomedical Aging Research, University of Innsbruck, Innsbruck, Austria.
Front Immunol. 2022 Aug 16;13:845235. doi: 10.3389/fimmu.2022.845235. eCollection 2022.
B cells are key mediators of humoral immunity. Mature B cells fall into various sub-classes that can be separated by their ontogeny, expression of cell surface markers, anatomical location, and function. B1 subsets play important roles in natural immunity and constitute the majority of B cells in newborns. In the adult, B1 cells predominate in the pleural and peritoneal cavities, while the mature B2 follicular subset makes up the major fraction of B cells in lymphoid tissue, although important subsets of antibody-secreting B1 cells are also present at these sites. B1 cells are the main producers of natural IgM but can also contribute to elimination of some pathogens, while B2 cells primarily mediate response to foreign antigens. The differential molecular underpinning of the B1 and B2 subsets remains incompletely understood. Here we demonstrate that germline-deficiency of the orphan nuclear receptor NR2F6 causes a partial loss of B1b and B2 B cells in the peritoneum while leaving peritoneal B1a cells unaltered. A competitive bone marrow chimera in host mice produced similar numbers of and peritoneal B1b and B2 cells. The proliferation of peritoneal B cells was not altered, while the migration marker CXCR5 was reduced on all subsets but Beta7-integrin was reduced only on peritoneal B1b and B2 cells. Similarly, B1b and B2 but not B1a cells, exhibited significantly reduced survival.
B 细胞是体液免疫的关键介质。成熟 B 细胞分为多个亚类，可根据其发生、表面标记物表达、解剖位置和功能进行区分。B1 亚群在天然免疫中发挥重要作用，构成新生儿 B 细胞的大部分。在成人中，B1 细胞主要存在于胸膜和腹膜腔中，而成熟的 B2 滤泡亚群构成淋巴组织中 B 细胞的主要部分，尽管这些部位也存在重要的分泌抗体的 B1 细胞亚群。B1 细胞是天然 IgM 的主要产生者，但也可以有助于清除一些病原体，而 B2 细胞主要介导对外来抗原的反应。B1 和 B2 亚群的差异分子基础仍不完全清楚。在这里，我们证明了孤儿核受体 NR2F6 的种系缺失导致腹膜中 B1b 和 B2 B 细胞的部分缺失，而腹膜中 B1a 细胞未受影响。在宿主小鼠中进行的竞争性骨髓嵌合体产生了数量相似的 和 腹膜 B1b 和 B2 细胞。 腹膜 B 细胞的增殖未改变，而迁移标记物 CXCR5 在所有亚群上减少，但 Beta7-整联蛋白仅在腹膜 B1b 和 B2 细胞上减少。同样，B1b 和 B2 但不是 B1a 细胞表现出明显降低的存活率。
