The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria 3052, Australia; Department of Medical Biology, The University of Melbourne, Parkville, Victoria 3010, Australia.
The University of Melbourne, Department of Microbiology and Immunology, The Peter Doherty Institute for Infection and Immunity, 792 Elizabeth Street, Melbourne, Victoria 3000, Australia.
Cell Rep. 2019 Nov 19;29(8):2257-2269.e6. doi: 10.1016/j.celrep.2019.10.087.
Despite the key role that antibodies play in protection, the cellular processes mediating the acquisition of humoral immunity against malaria are not fully understood. Using an infection model of severe malaria, we find that germinal center (GC) B cells upregulate the transcription factor T-bet during infection. Molecular and cellular analyses reveal that T-bet in B cells is required not only for IgG switching but also favors commitment of B cells to the dark zone of the GC. T-bet was found to regulate the expression of Rgs13 and CXCR3, both of which contribute to the impaired GC polarization observed in the absence of T-bet, resulting in reduced IghV gene mutations and lower antibody avidity. These results demonstrate that T-bet modulates GC dynamics, thereby promoting the differentiation of B cells with increased affinity for antigen.
尽管抗体在保护中起着关键作用，但介导针对疟疾的体液免疫获得的细胞过程尚未完全了解。我们使用严重疟疾感染模型发现，生发中心（GC）B 细胞在感染过程中上调转录因子 T-bet。分子和细胞分析表明，B 细胞中的 T-bet 不仅需要 IgG 转换，而且有利于 B 细胞向 GC 的暗区的定型。发现 T-bet 调节 Rgs13 和 CXCR3 的表达，这两者都有助于观察到的缺乏 T-bet 时 GC 极化受损，导致 IghV 基因突变减少和抗体亲和力降低。这些结果表明 T-bet 调节 GC 动力学，从而促进对抗原具有更高亲和力的 B 细胞分化。
