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Dynamic encounters with red blood cells trigger splenic marginal zone B cell retention and function
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Dynamic encounters with red blood cells trigger splenic marginal zone B cell retention and function
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Dynamic encounters with red blood cells trigger splenic marginal zone B cell retention and function
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Journal Article
Dynamic encounters with red blood cells trigger splenic marginal zone B cell retention and function
2024
Overview
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 Gα
13
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.
Cyster and colleagues show that CD97–CD55 interactions, which trigger Gα
13
–ARHGEF–Rho cytoskeletal signaling, are needed for proper MZ B cell positioning/retention in the spleen and for optimal antibody responses to T cell-independent antigens.
