Uptake and presentation of myelin basic protein by normal human B cells

Area of Science:

• Immunology
• Autoimmune Diseases
• Cell Biology

Background:

• B cells have dual roles in T-cell mediated autoimmune diseases, including multiple sclerosis (MS).
• Their functions are linked to antigen binding and presentation capabilities.
• Self-antigen presentation by B cells is crucial for understanding immune tolerance and disease pathogenesis.

Purpose of the Study:

• To investigate the mechanisms of B cell binding and presentation of the MS-associated self-antigen myelin basic protein (MBP).
• To determine the role of serum and complement receptors in this process.
• To explore the immunoregulatory potential of B cells presenting MBP-derived peptides.

Main Methods:

• Flow cytometry using mAb MK16 to detect MBP85-99 peptide presentation by B cells.
• Analysis of B cell binding and presentation under serum-free and serum-containing conditions.
• Assessment of complement receptor (CR1, CR2) involvement and B cell surface marker expression (CD27, CD86).
• Quantification of IL-10 producing CD4+ T cells after co-culture with MBP-pulsed B cells.

Main Results:

• Under serum-free conditions, 3-4% of B cells bound MBP and presented MBP85-99.
• Serum significantly increased MBP binding (complement-dependent) and MBP85-99 presentation in nearly half of B cells.
• Complement receptor 2 (CR2, CD21) was critical for MBP presentation, while CR1 (CD35) contributed to binding.
• MBP-presenting B cells often expressed CD27 and higher CD86 levels.
• MBP-pulsed B cells induced IL-10 producing CD4+ T cells in some donors, suggesting immunoregulatory capacity.

Conclusions:

• B cell presentation of MBP does not solely rely on specific B cell receptors, challenging existing assumptions.
• Complement-mediated mechanisms significantly enhance B cell antigen presentation in the presence of serum.
• These findings highlight a potential immunoregulatory role for B cells in autoimmune diseases like MS, influencing both tolerance and T cell responses.