The Francis Crick Institute, London, UK.
Imperial College, London, UK.
J Exp Med. 2021 Feb 1;218(2). doi: 10.1084/jem.20191393.
Memory B cells (MBCs) are long-lived cells that form a critical part of immunological memory, providing rapid antibody responses to recurring infections. However, very little is known about signals controlling MBC survival. Previous work has shown that antigen is not required for MBC survival, but a requirement for the B cell antigen receptor (BCR) has not been tested. Other studies have shown that, unlike naive B cells, MBCs do not express BAFFR and their survival is independent of BAFF, the ligand for BAFFR. Here, using inducible genetic ablation, we show that survival of MBCs is critically dependent on the BCR and on signaling through the associated CD79A protein. Unexpectedly, we found that MBCs express BAFFR and that their survival requires BAFF and BAFFR; hence, loss of BAFF or BAFFR impairs recall responses. Finally, we show that MBC survival requires IKK2, a kinase that transduces BAFFR signals. Thus, MBC survival is critically dependent on signaling from BCR and BAFFR.
记忆 B 细胞（MBC）是寿命较长的细胞，是免疫记忆的重要组成部分，可对反复感染迅速产生抗体反应。然而，关于控制 MBC 存活的信号知之甚少。以前的工作表明抗原不是 MBC 存活所必需的，但尚未测试 B 细胞抗原受体（BCR）的需求。其他研究表明，与幼稚 B 细胞不同，MBC 不表达 BAFFR，其存活不依赖于 BAFFR 的配体 BAFF。在这里，我们使用可诱导的遗传消融，显示 MBC 的存活严重依赖于 BCR 和相关的 CD79A 蛋白的信号转导。出乎意料的是，我们发现 MBC 表达 BAFFR，其存活需要 BAFF 和 BAFFR；因此，BAFF 或 BAFFR 的缺失会损害回忆反应。最后，我们发现 MBC 的存活需要 IKK2，一种转导 BAFFR 信号的激酶。因此，MBC 的存活严重依赖于 BCR 和 BAFFR 的信号转导。
