Department of Biochemistry and Molecular Biology, University of Calgary, Alberta T2N 4N1, Canada.
J Immunol. 2013 Sep 15;191(6):3112-8. doi: 10.4049/jimmunol.1202098. Epub 2013 Aug 21.
CD20 is a tetraspanning membrane protein expressed on B lymphocytes. CD20 deficiency in both mice and humans has recently been shown to have deleterious effects on Ab responses to T-independent Ags; however, no effect on T-dependent immunity has been reported. In this study, we used a Cd20⁻/⁻ mouse line to evaluate Ab responses to adeno-associated virus and SRBCs. The neutralizing Ab response to adeno-associated virus was significantly reduced by CD20 deficiency; both primary (IgM) and secondary (IgG1 and IgG2b) responses to SRBC were also reduced in Cd20⁻/⁻ mice, and this was associated with a reduction in the number of germinal center B cells. A successful humoral response requires the integration of intracellular signaling networks that critically rely on calcium mobilization. In this article, we confirm that BCR-mediated calcium mobilization is reduced in Cd20⁻/⁻ murine B cells after BCR stimulation in vitro, and further show that the reduction is due to an effect on calcium influx rather than calcium release from intracellular stores. Calcium-dependent upregulation of CD69 was impaired in CD20-deficient B cells, as was upregulation of CD86. Altogether, this study demonstrates a role for CD20 in B cell activation and T-dependent humoral immunity.
CD20 是一种表达在 B 淋巴细胞上的四跨膜蛋白。最近的研究表明，CD20 在人和小鼠中的缺失对 T 细胞非依赖抗原的 Ab 反应有有害影响；然而，尚未报道其对 T 细胞依赖免疫的影响。在这项研究中，我们使用 Cd20⁻/⁻ 小鼠品系来评估对腺相关病毒和 SRBC 的 Ab 反应。CD20 缺失显著降低了对腺相关病毒的中和 Ab 反应；Cd20⁻/⁻ 小鼠对 SRBC 的原发性（IgM）和次级（IgG1 和 IgG2b）反应也降低，这与生发中心 B 细胞数量减少有关。成功的体液反应需要整合细胞内信号网络，这对钙动员至关重要。在本文中，我们证实了 BCR 介导的钙动员在体外 BCR 刺激后在 Cd20⁻/⁻ 小鼠 B 细胞中减少，并且进一步表明这种减少是由于对钙内流的影响而不是细胞内储存的钙释放。钙依赖性 CD69 的上调在 CD20 缺陷 B 细胞中受损，CD86 的上调也是如此。总之，这项研究表明 CD20 在 B 细胞激活和 T 细胞依赖的体液免疫中起作用。
