Department of Microbiology and Immunology, Virginia Commonwealth University School of Medicine, Richmond, Virginia, United States of America.
PLoS One. 2013 Apr 8;8(4):e60640. doi: 10.1371/journal.pone.0060640. Print 2013.
The generation of antigen-specific antibodies and the development of immunological memory require collaboration between B and T cells. T cell-secreted IL-4 is important for B cell survival, isotype switch to IgG1 and IgE, affinity maturation, and the development of germinal centers (GC). Fyn, a member of the Src family tyrosine kinase, is widely expressed in many cell types, including lymphocytes. This kinase is known to interact with both the B cell and T cell receptor (BCR and TCR, respectively). While Fyn deletion does not impair the development of immature T cells and B cells, TCR signaling is altered in mature T cells. The current study demonstrates that Fyn deficient (KO) B cells have impaired IL-4 signaling. Fyn KO mice displayed low basal levels of IgG1, IgE and IgG2c, and delayed antigen-specific IgG1 and IgG2b production, with a dramatic decrease in antigen-specific IgG2c following immunization with a T-dependent antigen. Defects in antibody production correlated with significantly reduced numbers of GC B cells, follicular T helper cells (TFH), and splenic plasma cells (PC). Taken together, our data demonstrate that Fyn kinase is required for optimal humoral responses.
产生抗原特异性抗体和免疫记忆的发展需要 B 细胞和 T 细胞之间的协作。T 细胞分泌的 IL-4 对于 B 细胞的存活、同种型转换为 IgG1 和 IgE、亲和力成熟以及生发中心（GC）的发育是重要的。Src 家族酪氨酸激酶的成员 Fyn 在包括淋巴细胞在内的许多细胞类型中广泛表达。这种激酶已知与 B 细胞和 T 细胞受体（BCR 和 TCR，分别）相互作用。虽然 Fyn 缺失不会损害未成熟 T 细胞和 B 细胞的发育，但成熟 T 细胞中的 TCR 信号转导发生改变。本研究表明 Fyn 缺陷（KO）B 细胞的 IL-4 信号受损。Fyn KO 小鼠表现出低基础水平的 IgG1、IgE 和 IgG2c，以及抗原特异性 IgG1 和 IgG2b 产生延迟，用 T 依赖性抗原免疫后抗原特异性 IgG2c 显著减少。抗体产生的缺陷与 GC B 细胞、滤泡辅助性 T 细胞（TFH）和脾脏浆细胞（PC）的数量显著减少相关。总之，我们的数据表明 Fyn 激酶是产生最佳体液反应所必需的。
