{Reference Type}: Journal Article {Title}: Dynamic encounters with red blood cells trigger splenic marginal zone B cell retention and function. {Author}: Liu D;Winer BY;Chou MY;Tam H;Xu Y;An J;Gardner JM;Cyster JG; {Journal}: Nat Immunol {Volume}: 25 {Issue}: 1 {Year}: 2024 Jan 4 {Factor}: 31.25 {DOI}: 10.1038/s41590-023-01690-z {Abstract}: 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.