Review: B cells in MS

[NHE]

B cells in multiple sclerosis — from targeted depletion to immune reconstitution therapies
Nature Reviews Neurology, 2021;17(7):399–414.

Increasing evidence indicates the involvement of B cells in the pathogenesis of multiple sclerosis (MS), but their precise roles are unclear. In this Review, we provide an overview of the development and physiological functions of B cells and the main mechanisms through which B cells are thought to contribute to CNS autoimmunity. In MS, abnormalities of B cell function include pro-inflammatory cytokine production, defective B cell regulatory function and the formation of tertiary lymphoid-like structures in the CNS, which are the likely source of abnormal immunoglobulin production detectable in the cerebrospinal fluid. We also consider the hypothesis that Epstein–Barr virus (EBV) is involved in the B cell overactivation that leads to inflammatory injury to the CNS in MS. We also review the immunological effects — with a focus on the effects on B cell subsets — of several successful therapeutic approaches in MS, including agents that selectively deplete B cells (rituximab, ocrelizumab and ofatumumab), agents that less specifically deplete lymphocytes (alemtuzumab and cladribine) and autologous haematopoietic stem cell transplantation, in which the immune system is unselectively ablated and reconstituted. We consider the insights that these effects on B cell populations provide and their potential to further our understanding and targeting of B cells in MS.

Key points

• Accumulating neuropathological, serological and immune cellular evidence strongly suggests that B cells are involved in the pathophysiology of multiple sclerosis (MS).

• Specific B cell subsets seem to be involved in MS as antigen-presenting cells and pro-inflammatory cytokine-producing cells; other B cell subsets serve as anti-inflammatory regulatory cells.

• The persistently active infection of B cells with Epstein–Barr virus could lead to CNS damage; however, the causative role of the virus in MS remains controversial.

• Treatments that target B cells are effective in MS, which strongly suggests the involvement of B cells in disease pathophysiology.

• Autologous haematopoietic stem cell transplantation is known to have regenerative effects on T cells and limited evidence indicates that the treatment leads to repopulation with predominantly naive B cells.

• The effects of therapies on B cell subsets provide insight into the roles of B cell populations in disease; further immunological studies are required to improve our understanding of these roles.