Age-associated B cells (ABCs) develop from a CNS-localized progenitor pool into a pro-inflammatory phenotype after...

Area of Science:

• Neuroimmunology
• Immunosenology
• Stroke Research

Background:

• Aging and ischemic stroke promote chronic lymphocyte accumulation in the central nervous system (CNS).
• The immunophenotype of lymphocytes shifts with age and injury, impacting functional recovery after stroke.
• Understanding CNS-localized B cell subsets is crucial for deciphering their role in aging and stroke.

Purpose of the Study:

• To characterize CNS-localized B cell subsets in aged mice and humans.
• To identify novel B cell populations and their behavior following ischemic stroke.
• To investigate the conserved inflammatory signatures of these B cells across species.

Main Methods:

• Flow cytometry and single-cell RNA sequencing (scRNA-seq) were employed on B cells from aged mouse brains (uninjured and post-stroke).
• B cell receptor (BCR) sequencing was performed to analyze B cell clonality.
• Post-mortem human brain tissue from aged donors was analyzed for analogous B cell populations.

Main Results:

• A novel B1b cell progenitor pool, distinct from known niches, was identified within the CNS.
• Trajectory analysis revealed progenitor transition into age-associated B cell (ABC) subsets.
• Clonal expansion of IgM+ ABCs (ABC/B1b) and plasma cells was observed post-stroke.
• Analogous ABCs and developing B cells were confirmed in aged human brain tissue.

Conclusions:

• Unique B cell populations capable of proliferating within the aging CNS were discovered.
• Age-associated B cells (ABCs) and their progenitors exhibit conserved inflammatory signatures across species.
• These findings offer new insights into B cell dynamics in the aging brain and after stroke.