jem_20191393.pdf (6.09 MB)
Critical requirement for BCR, BAFF, and BAFFR in memory B cell survival
journal contributionposted on 2020-10-30, 14:47 authored by Jennifer Müller-Winkler, Richard Mitter, Julie CF Rappe, Lesley Vanes, Edina Schweighoffer, Hamid Mohammadi, Andreas Wack, Victor LJ Tybulewicz
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.
Crick (Grant ID: 10206, Grant title: Wack FC001206) Crick (Grant ID: 10194, Grant title: Tybulewicz FC001194)