1. Academic Validation
  2. B cell-intrinsic requirement for WNK1 kinase in antibody responses in mice

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

Affiliations

  • 1 The Francis Crick Institute , London, UK.
  • 2 Department of Oncology, Microbiology and Immunology, University of Fribourg , Fribourg, Switzerland.
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.

Figures
Products