Critical requirement for BCR, BAFF, and BAFFR in memory B cell survival.

Critical requirement for BCR, BAFF, and BAFFR in memory B cell survival.
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DOI:
10.1084/jem.20191393
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发表时间:
2021-02-01
期刊:
The Journal of experimental medicine
影响因子:
--
通讯作者:
Tybulewicz VLJ
Tybulewicz VLJ
中科院分区:
其他
文献类型:
--
作者:
Müller-Winkler J;Mitter R;Rappe JCF;Vanes L;Schweighoffer E;Mohammadi H;Wack A;Tybulewicz VLJ

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记忆B细胞是体液免疫记忆的长寿成分。Müller-Winkler等人表明,MBC的存活严重依赖于来自BCR、BAFF、BAFFR和IKK 2激酶的信号传导。记忆B细胞(MBC)是形成免疫记忆的关键部分的长寿细胞,提供对复发感染的快速抗体应答。然而,对控制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,但尚未测试对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,并且它们的存活不依赖于BAFFR的配体BAFF。在这里,使用诱导基因消融,我们表明,MBCs的生存是严重依赖于BCR和信号通过相关的CD 79 A蛋白。出乎意料的是,我们发现MBC表达BAFFR,并且它们的存活需要BAFF和BAFFR;因此,BAFF或BAFFR的缺失会损害回忆反应。最后,我们表明MBC的生存需要IKK 2,一种转导BAFFR信号的激酶。因此,MBC存活严重依赖于来自BCR和BAFFR的信号传导。
Memory B cells are long-lived components of humoral immunological memory. Müller-Winkler et al. show that the survival of MBCs is critically dependent on signaling from the BCR, BAFF, BAFFR, and IKK2 kinase. 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.
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