jem_20211827.pdf (6.92 MB)
B cell-intrinsic requirement for WNK1 kinase in antibody responses in mice.
journal contributionposted on 2023-01-23, 10:37 authored by Darryl A Hayward, Lesley Vanes, Stefanie Wissmann, Sujana Sivapatham, Harald Hartweger, Joshua Biggs O'May, Leonard L de Boer, Richard Mitter, Robert Köchl, Jens V Stein, Victor LJ Tybulewicz
Migration and adhesion play critical roles in B cells, regulating recirculation between lymphoid organs, migration within lymphoid tissue, and interaction with CD4+ T cells. However, there is limited knowledge of how B cells integrate chemokine receptor and integrin signaling with B cell activation to generate efficient humoral responses. Here, we show that the WNK1 kinase, a regulator of migration and adhesion, is essential in B cells for T-dependent and -independent antibody responses. We demonstrate that WNK1 transduces signals from the BCR, CXCR5, and CD40, and using intravital imaging, we show that WNK1 regulates migration of naive and activated B cells, and their interactions with T cells. Unexpectedly, we show that WNK1 is required for BCR- and CD40-induced proliferation, acting through the OXSR1 and STK39 kinases, and for efficient B cell-T cell collaboration in vivo. Thus, WNK1 is critical for humoral immune responses, by regulating B cell migration, adhesion, and T cell-dependent activation.
Crick (Grant ID: CC1107, Grant title: STP Bioinformatics & Biostatistics) Crick (Grant ID: CC2080, Grant title: Tybulewicz CC2080)