Dual Role of B Cells in Multiple Sclerosis

B cells have emerged as an important immune cell type that can be targeted for therapy in multiple sclerosis (MS). Depleting B cells with anti-CD20 antibodies is effective in treating MS. Yet, atacicept treatment, which blocks B-cell Activating Factor (BAFF) and A Proliferation-Inducing Ligand (APRIL), two cytokines important for B cell development and function, paradoxically increases disease activity in MS patients. The reason behind the failure of atacicept is not well understood. The stark differences in clinical outcomes with these therapies demonstrate that B cells have both inflammatory and anti-inflammatory functions in MS. In this review, we summarize the importance of B cells in MS and discuss the different B cell subsets that perform inflammatory and anti-inflammatory functions and how therapies modulate B cell functions in MS patients. Additionally, we discuss the potential anti-inflammatory functions of BAFF and APRIL on MS disease.

Automated summary

B cells have emerged as important immune cells in multiple sclerosis (MS) and can be targeted for therapy. Depleting B cells with anti-CD20 antibodies is effective, but blocking B-cell Activating Factor (BAFF) and A Proliferation-Inducing Ligand (APRIL) with atacicept paradoxically increases disease activity in MS patients. The reasons for this failure are not well understood. Clinical outcomes with these therapies illustrate that B cells have both inflammatory and anti-inflammatory functions in MS. This review summarizes the importance of B cells in MS, discusses different B cell subsets and their functions, and explores how therapies modulate B cell functions in MS patients. The potential anti-inflammatory functions of BAFF and APRIL in MS disease are also discussed.