Sugiyama Yuma, Fujiwara Mitsuhiro, Sakamoto Akihiko, Tsushima Hiromichi, Nishikimi Akihiko, Maruyama Mitsuo
Department of Inflammation and Immunosenescence, Geroscience Research Center, Research Institute, National Center for Geriatrics and Gerontology, 7-430 Morioka-cho, Obu, Aichi, 474-8511, Japan.
Biosafety Division, Research Institute, National Center for Geriatrics and Gerontology, Obu, Aichi, Japan.
Immun Ageing. 2022 Jan 3;19(1):2. doi: 10.1186/s12979-021-00259-4.
Memory B cells are an antigen-experienced B-cell population with the ability to rapidly differentiate into antibody-producing cells by recall responses. We recently found that dedicator of cytokinesis 11 (DOCK11) contributes to the expansion of antigen-specific populations among germinal center B cells upon immunization. In comparison, limited information is available on the contribution of DOCK11 to secondary humoral immune responses.
In this study, effects of the DOCK11 deficiency in B cells were examined on secondary immune responses to protein antigen. The lack of DOCK11 in B cells resulted in the impaired induction of antibody-producing cells upon secondary immunization with protein antigen. DOCK11 was dispensable for the recall responses of antigen-experienced B cells, as demonstrated by the comparable induction of antibody-producing cells in mice given transfer of antigen-experienced B cells with no DOCK11 expression. Instead, the lack of DOCK11 in B cells resulted in the impaired secondary immune responses in a B cell-extrinsic manner, which was recovered by the adoptive transfer of cognate T cells.
We addressed that intrinsic and extrinsic effects of DOCK11 expression in B cells may contribute to secondary humoral immune responses in manner of the induction of cognate T-cell help.
记忆B细胞是一群经历过抗原刺激的B细胞，能够通过回忆反应迅速分化为产生抗体的细胞。我们最近发现，胞质分裂 dedicator 11（DOCK11）在免疫后有助于生发中心B细胞中抗原特异性群体的扩增。相比之下，关于DOCK11对二次体液免疫反应的贡献的信息有限。
在本研究中，研究了B细胞中DOCK11缺陷对蛋白质抗原二次免疫反应的影响。B细胞中缺乏DOCK11导致在用蛋白质抗原进行二次免疫时产生抗体的细胞诱导受损。DOCK11对于经历过抗原刺激的B细胞的回忆反应是可有可无的，这在接受无DOCK11表达的经历过抗原刺激的B细胞转移的小鼠中产生抗体的细胞的可比诱导中得到了证明。相反，B细胞中缺乏DOCK11以B细胞外在方式导致二次免疫反应受损，通过同源T细胞的过继转移得以恢复。
我们指出，B细胞中DOCK11表达的内在和外在作用可能通过诱导同源T细胞帮助的方式促进二次体液免疫反应。
