Cytotoxic B Cells in Relapsing-Remitting Multiple Sclerosis Patients

Area of Science:

• Immunology
• Neuroimmunology
• Cell Biology

Background:

• Multiple Sclerosis (MS) pathogenesis involves complex immune cell interactions.
• Emerging evidence suggests B cells have antibody-independent roles in MS.
• The efficacy of anti-CD20 therapies prompts re-evaluation of B cell contributions to MS.

Purpose of the Study:

• To investigate if CD19+ B cells express granzyme-B (GzmB) in relapsing-remitting MS (RRMS) patients.
• To compare GzmB expression in B cells with cytotoxic CD8+ T lymphocytes.
• To assess B cell cytotoxic potential in RRMS patients undergoing various treatments.

Main Methods:

• Flow cytometry was used to analyze CD8, CD19, Runx3, and GzmB expression.
• Included 104 RRMS patients on different treatments and 58 healthy donors.
• Compared GzmB expression in CD19+ B cells across treatment groups and controls.

Main Results:

• RRMS patients on fingolimod (FTY) and natalizumab (NTZ) showed increased CD8+GzmB+ T cells versus healthy donors.
• Increased CD19+GzmB+ B cells were observed in RRMS patients on FTY and NTZ compared to glatiramer, untreated RRMS, and healthy donors.
• GzmB expression was significantly higher in CD19+Runx3+ B cells than CD19+Runx3- B cells in RRMS patients.

Conclusions:

• CD19+ B cells in MS patients under certain treatments may exhibit cytotoxic activity akin to CD8+ T lymphocytes.
• Monitoring these "cytotoxic" B cell subsets could aid MS pathophysiology research.
• This approach may inform the development of novel therapeutic strategies for MS.