Published on Thu Sep 09 2021

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

Hayward, D., Vanes, L., Wissmann, S., Sivapatham, S., Hartweger, H., Biggs O'May, J., De Boer, L., Mitter, R., Kochl, R., Stein, J. V., Tybulewicz, V. L.

Migration and adhesion play critical roles in B cells, regulating recirculation between lymphoid organs and interaction with CD4+ T cells. There is limited knowledge of how B cells integrate chemokine receptor and integrin signaling with B cell activation to generate efficient humoral responses.

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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 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.