%0 Journal Article
%T Dynamic encounters with red blood cells trigger splenic marginal zone B cell retention and function.
%A Liu D
%A Winer BY
%A Chou MY
%A Tam H
%A Xu Y
%A An J
%A Gardner JM
%A Cyster JG
%J Nat Immunol
%V 25
%N 1
%D 2024 Jan 4
%M 38049580
%F 31.25
%R 10.1038/s41590-023-01690-z
%X Spleen 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.