Institute of Immunology, Jena University Hospital, Jena, Germany.
PLoS One. 2011;6(9):e24718. doi: 10.1371/journal.pone.0024718. Epub 2011 Sep 8.
The therapeutic benefit of B cell depletion in patients with rheumatoid arthritis has provided proof of concept that B cells are relevant for the pathogenesis of arthritis. It remains unknown which B cell effector functions contribute to the induction or chronification of arthritis. We studied the clinical and immunological effects of B cell depletion in glucose-6-phosphate isomerase-induced arthritis. We targeted CD22 to deplete B cells. Mice were depleted of B cells before or after immunization with glucose-6-phosphate isomerase (G6PI). The clinical and histological effects were studied. G6PI-specific antibody responses were measured by ELISA. G6PI-specific T helper (Th) cell responses were assayed by polychromatic flow cytometry. B cell depletion prior to G6PI-immunization prevented arthritis. B cell depletion after immunization ameliorated arthritis, whereas B cell depletion in arthritic mice was ineffective. Transfer of antibodies from arthritic mice into B cell depleted recipients did not reconstitute arthritis. B cell depleted mice harbored much fewer G6PI-specific Th cells than control animals. B cell depletion prevents but does not cure G6PI-induced arthritis. Arthritis prevention upon B cell depletion is associated with a drastic reduction in the number of G6PI-specific effector Th cells.
B 细胞耗竭在类风湿关节炎患者中的治疗益处提供了证据，证明 B 细胞与关节炎的发病机制有关。目前尚不清楚哪些 B 细胞效应功能有助于关节炎的诱导或慢性化。我们研究了葡萄糖-6-磷酸异构酶诱导关节炎中 B 细胞耗竭的临床和免疫学效应。我们针对 CD22 来耗竭 B 细胞。在葡萄糖-6-磷酸异构酶（G6PI）免疫之前或之后，用 G6PI 耗竭 B 细胞。研究了临床和组织学效应。通过 ELISA 测量 G6PI 特异性抗体反应。通过多色流式细胞术测定 G6PI 特异性辅助性 T 细胞（Th）反应。在 G6PI 免疫之前耗竭 B 细胞可预防关节炎。免疫后耗竭 B 细胞可改善关节炎，而关节炎小鼠中的 B 细胞耗竭则无效。将来自关节炎小鼠的抗体转移到 B 细胞耗竭的受者中不会重建关节炎。与对照动物相比，B 细胞耗竭的小鼠中 G6PI 特异性 Th 细胞少得多。B 细胞耗竭可预防但不能治愈 G6PI 诱导的关节炎。B 细胞耗竭预防关节炎与 G6PI 特异性效应 Th 细胞数量的急剧减少有关。
