B cell-intrinsic requirement for WNK1 kinase in antibody responses in mice

  • J Exp Med. 2023 Mar 6;220(3):e20211827. doi: 10.1084/jem.20211827.
Darryl A Hayward  1 ,  Lesley Vanes  1 ,  Stefanie Wissmann  2 ,  Sujana Sivapatham  2 ,  Harald Hartweger  1 ,  Joshua Biggs O'May  1 ,  Leonard L de Boer  1 ,  Richard Mitter  1 ,  Robert Köchl  1 ,  Jens V Stein  2 ,  Victor L J Tybulewicz  1
Affiliations
  • 1. The Francis Crick Institute , London, UK.
  • 2. Department of Oncology, Microbiology and Immunology, University of Fribourg , Fribourg, Switzerland.
PMID: 36662229 DOI: 10.1084/jem.20211827
Abstract

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.

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