B cell-intrinsic requirement for WNK1 kinase in T cell-dependent antibody responses

• Published in: bioRxiv
• Main Authors: Hayward, Darryl, Vanes, Lesley, Wissmann, Stefanie, Sivapatham, Sujana, Hartweger, Harald, Joshua Biggs O'may, De Boer, Leon, Mitter, Richard, Kochl, Robert, Stein, Jens V, Tybulewicz, Victor Lj
• Format: Paper
• Language: English
• Published: Cold Spring Harbor Cold Spring Harbor Laboratory Press 09.09.2021
• Subjects: CD4 antigen; CD40 antigen; Cell activation; Cell migration; Chemokine receptors; CXCR5 protein; Immune response (humoral); Lymphocytes; Lymphocytes B; Lymphocytes T; Lymphoid tissue
• DOI: 10.1101/2021.09.09.459588

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 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. Competing Interest Statement The authors have declared no competing interest.