Dynamic encounters with red blood cells trigger splenic marginal zone B cell retention and function

Author:

Liu DanORCID,Winer Benjamin Y.,Chou Marissa Y.,Tam HansonORCID,Xu Ying,An Jinping,Gardner James M.ORCID,Cyster Jason G.ORCID

Abstract

AbstractSpleen marginal zone (MZ) B cells are important for antibody responses against blood-borne antigens. The signals they use to detect exposure to blood are not well defined. Here, using intravital two-photon microscopy in mice, we observe transient contacts between MZ B cells and red blood cells that are in flow. We show that MZ B cells use adhesion G-protein-coupled receptor ADGRE5 (CD97) for retention in the spleen. CD97 function in MZ B cells depends on its ability to undergo autoproteolytic cleavage and signaling via Gα13 and ARHGEF1. Red blood cell expression of the CD97 ligand CD55 is required for MZ B cell homeostasis. Applying a pulling force on CD97-transfected cells using an optical C-trap and CD55+ beads leads to accumulation of active RhoA and membrane retraction. Finally, we show that CD97 deficiency leads to a reduced T cell-independent IgM response. Thus, our studies provide evidence that MZ B cells use mechanosensing to position in a manner that enhances antibody responses against blood-borne antigens.

Funder

U.S. Department of Health & Human Services | National Institutes of Health

Cancer Research Institute

Schmidt Science Fellowship

Publisher

Springer Science and Business Media LLC

Subject

Immunology,Immunology and Allergy

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