Charité Universitätsmedizin, Klinik mit Schwerpunkt Rheumatologie und klinische Immunologie, Berlin, Germany.
Eur J Immunol. 2010 Jun;40(6):1809-18. doi: 10.1002/eji.200940050.
B1a B cells have been implicated in the pathogenesis of systemic lupus erythematosus; however, their precise contribution to the disease remains unclear. Here we analysed isotype expression, organ accumulation and autoreactivity of B1a cells in the NZB/W F1 murine model for systemic lupus erythematosus using flow cytometry, ELISPOT and adoptive cell transfer. In the course of lupus, the B1a compartment is expanded and B1a cells class switch to IgG. Class-switched B1a B cells were excluded from the peritoneal cavity but accumulated in the spleen and target organs such as kidneys and thymus. Autoreactive B1a B cells preferentially class switch, which leads to a subsequent loss of autoreactive B1a cells from the peritoneal cavity. We propose a model whereby autoreactive B1a B cells become activated early in the course of lupus and class switch to IgG. These autoreactive B1a B cells accumulate in the spleen and affected organs where they presumably secrete autoantibodies and contribute to the local and systemic pathogenesis.
B1a 细胞被认为与系统性红斑狼疮的发病机制有关；然而，它们对疾病的确切贡献仍不清楚。在这里，我们使用流式细胞术、ELISPOT 和过继细胞转移分析了 NZB/W F1 系统性红斑狼疮小鼠模型中 B1a 细胞的同种型表达、器官积累和自身反应性。在狼疮的发展过程中，B1a 细胞群被扩增，B1a 细胞发生免疫球蛋白类别转换。发生类别转换的 B1a B 细胞被排除出腹腔，但在脾脏和肾脏、胸腺等靶器官中积累。自身反应性 B1a B 细胞优先发生类别转换，导致腹腔中自身反应性 B1a 细胞随后减少。我们提出了一个模型，即自身反应性 B1a B 细胞在狼疮早期被激活并发生免疫球蛋白类别转换。这些自身反应性 B1a B 细胞在脾脏和受影响的器官中积累，推测它们在那里分泌自身抗体并有助于局部和全身发病机制。
