Immunology Division, Garvan Institute of Medical Research, Darlinghurst, New South Wales, Australia.
St. Vincent's Clinical School, University of New South Wales, Darlinghurst, New South Wales, Australia.
J Exp Med. 2021 Feb 1;218(2). doi: 10.1084/jem.20191167.
The TNF superfamily ligand BAFF maintains the survival of naive B cells by signaling through its surface receptor, BAFFR. Activated B cells maintain expression of BAFFR after they differentiate into germinal center (GC) or memory B cells (MBCs). However, the functions of BAFFR in these antigen-experienced B cell populations remain unclear. Here, we show that B cell-intrinsic BAFFR does not play a significant role in the survival or function of GC B cells or in the generation of the somatically mutated MBCs derived from them. Instead, BAFF/BAFFR signaling was required to generate the unmutated, GC-independent MBCs that differentiate directly from activated B cell blasts early in the response. Furthermore, amplification of BAFFR signaling in responding B cells did not affect GCs or the generation of GC-derived MBCs but greatly expanded the GC-independent MBC response. Although BAFF/BAFFR signaling specifically controlled the formation of the GC-independent MBC response, both types of MBCs required input from this pathway for optimal long-term survival.
TNF 超家族配体 BAFF 通过其表面受体 BAFFR 信号转导来维持初始 B 细胞的存活。活化的 B 细胞在分化为生发中心 (GC) 或记忆 B 细胞 (MBC) 后仍表达 BAFFR。然而，BAFFR 在这些抗原经历的 B 细胞群体中的功能仍不清楚。在这里，我们表明，内在的 B 细胞 BAFFR 对于 GC B 细胞的存活或功能，或源自它们的体细胞突变的 MBC 的产生没有显著作用。相反，BAFF/BAFFR 信号对于从激活的 B 细胞爆发生成直接分化的未突变、GC 非依赖的 MBC 是必需的。此外，在反应早期，响应 B 细胞中 BAFFR 信号的扩增不会影响 GC 或 GC 衍生的 MBC 的产生，但大大扩展了 GC 非依赖的 MBC 反应。尽管 BAFF/BAFFR 信号特异性地控制 GC 非依赖的 MBC 反应的形成，但这两种类型的 MBC 都需要该途径的输入以实现最佳的长期存活。
