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

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.

T cell migration requires ion and water influx to regulate actin polymerization

“…We previously showed that loss of WNK1 slows down the homing of both CD4 + and CD8 + T cells to secondary lymphoid organs, and impairs CXCL12-induced migration of CD4 - CD8 - thymocytes 6, 28 . More recently we found that WNK1 is required for CXCL13-induced migration of B cells and their in vivo migration in lymph nodes 29 . Furthermore, previous studies have shown that inhibition of the sodium-hydrogen exchanger NHE-1 (SLC9A1) or AQP9 decreases fMLP-induced migration of human neutrophils, and SLC12A2 inhibition reduces migration of glioblastoma cells, indicating that ion and water movement may be important for migration in multiple contexts 30–32 .…”