Authors: | Liu, D.; Winer, B. Y.; Chou, M. Y.; Tam, H.; Xu, Y.; An, J.; Gardner, J. M.; Cyster, J. G. |
Article Title: | Dynamic encounters with red blood cells trigger splenic marginal zone B cell retention and function |
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. © 2023, The Author(s). |
Keywords: | signal transduction; controlled study; unclassified drug; human cell; nonhuman; antigen expression; t lymphocyte; animal cell; mouse; animal; metabolism; animals; mice; cell function; spleen; protein degradation; b lymphocyte; b-lymphocytes; genetic transfection; rhoa guanine nucleotide binding protein; erythrocyte; homeostasis; lymphoid tissue; intravital microscopy; multiphoton microscopy; cell interaction; g protein coupled receptor; protein cleavage; erythrocytes; immunoglobulin m; spleen cell; mechanotransduction; cell contact; guanine nucleotide binding protein alpha subunit; decay accelerating factor; human; article; cd55 antigens; cd97 antigen; guanine nucleotide binding protein alpha subunit 13; spleen marginal zone b cell |
Journal Title: | Nature Immunology |
Volume: | 25 |
Issue: | 1 |
ISSN: | 1529-2908 |
Publisher: | Nature Publishing Group |
Date Published: | 2024-01-01 |
Start Page: | 142 |
End Page: | 154 |
Language: | English |
DOI: | 10.1038/s41590-023-01690-z |
PUBMED: | 38049580 |
PROVIDER: | scopus |
PMCID: | PMC10761324 |
DOI/URL: | |
Notes: | Article -- Source: Scopus |