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Nature immunology
Jan, 2024;25 (1): 142-154.

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

Dan Liu, Benjamin Y Winer, Marissa Y Chou, Hanson Tam, Ying Xu, Jinping An, James M Gardner, Jason G Cyster
Author Information
  1. Dan Liu: Howard Hughes Medical Institute and Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA, USA. liudan@westlake.edu.cn. ORCID
  2. Benjamin Y Winer: Howard Hughes Medical Institute and Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA, USA.
  3. Marissa Y Chou: Howard Hughes Medical Institute and Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA, USA.
  4. Hanson Tam: Howard Hughes Medical Institute and Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA, USA. ORCID
  5. Ying Xu: Howard Hughes Medical Institute and Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA, USA.
  6. Jinping An: Howard Hughes Medical Institute and Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA, USA.
  7. James M Gardner: Diabetes Center and Department of Surgery, University of California, San Francisco, San Francisco, CA, USA. ORCID
  8. Jason G Cyster: Howard Hughes Medical Institute and Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA, USA. jason.cyster@ucsf.edu. ORCID
PMID: 38049580 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 Gα 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.

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Grants

  1. R01 AI040098/NIAID NIH HHS
  2. T32 GM141323/NIGMS NIH HHS
  3. R01 AI045073/NIAID NIH HHS
  4. P30 CA008748/NCI NIH HHS
  5. R37 AI045073/NIAID NIH HHS

MeSH Term

Mice
Animals
B-Lymphocytes
Lymphoid Tissue
Spleen
Signal Transduction
CD55 Antigens
Erythrocytes

Chemicals

CD55 Antigens
Journal Article
Article has an altmetric score of 14

Word Cloud

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