Cxcr4 desensitization is an essential regulatory mechanism controlling the extra-follicular B cell response.

Alouche, N.; Bonaud, A.; Rondeau, V.; Nguyen, J.; Cricks, E.; Setterblad, N.; Mahevas, M.; Balabanian, K.; Espeli, M.

doi:10.1101/537761

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bioRxiv · 10.1101/537761

Cxcr4 desensitization is an essential regulatory mechanism controlling the extra-follicular B cell response.

Alouche, N.·Bonaud, A.·Rondeau, V.·Nguyen, J.·Cricks, E.·Setterblad, N.·Mahevas, M.·Balabanian, K.·Espeli, M.

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Abstract

The signaling axis formed by the chemokine CXCL12 and its receptor CXCR4 plays an important role in B cell development and activation and is finely regulated by a process termed desensitization. Mutations leading to a truncation of the C-terminus tail of CXCR4 and thus to a defective desensitization have been reported in two diseases, a rare immunodeficiency called the WHIM syndrome and a B cell plasmacytoma called Waldenstroms Macroglobulinemia (WM). How CXCR4 desensitization may impact B cell activation in the context of a T-independent extra-follicular response is still unknown. Here using a unique mouse model bearing an orthologous gain of function mutation of Cxcr4 we report that Cxcr4 desensitization is an essential gatekeeper controlling B lymphocyte entry into cycle, plasma cell differentiation, migration and maturation upon Myd88-dependent signaling. Altogether, our results support an essential role for Cxcr4 desensitization in limiting the depth and width of the B cell extra-follicular response and PC development.

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Alouche, N., Bonaud, A., Rondeau, V., Nguyen, J., Cricks, E., Setterblad, N., Mahevas, M., Balabanian, K., Espeli, M.. 2019-02-01. Cxcr4 desensitization is an essential regulatory mechanism controlling the extra-follicular B cell response.. https://doi.org/10.1101/537761

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