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

Area of Science:

• Immunology
• Cell Biology
• Biophysics

Background:

• Spleen marginal zone (MZ) B cells are critical for antibody production against blood-borne pathogens.
• The mechanisms by which MZ B cells sense blood exposure remain poorly understood.

Purpose of the Study:

• To investigate the role of mechanosensing in MZ B cell function and positioning.
• To identify the molecular players involved in MZ B cell detection of blood-borne signals.

Main Methods:

• Intravital two-photon microscopy in mice to observe cell-cell interactions in vivo.
• Utilized optical C-trap assays to apply mechanical force on cells.
• Investigated signaling pathways including Gα13 and ARHGEF1.

Main Results:

• MZ B cells engage in transient contacts with flowing red blood cells.
• Adhesion G-protein-coupled receptor ADGRE5 (CD97) mediates MZ B cell retention in the spleen.
• CD97 signaling, dependent on autoproteolytic cleavage and Gα13/ARHGEF1, and CD55 on red blood cells are essential for MZ B cell homeostasis.
• Mechanical force on CD97 triggers RhoA activation and membrane retraction.
• CD97 deficiency impairs T cell-independent IgM responses.

Conclusions:

• MZ B cells employ mechanosensing through CD97 to sense blood flow and maintain splenic positioning.
• This mechanosensory mechanism is vital for effective antibody responses against blood-borne antigens.