Unraveling B-lymphocytes in CNS inflammatory diseases: Distinct mechanisms and treatment targets.

Klein da Costa, Bruna; Brant de Souza Melo, Renata; Rodrigues Dos Passos, Giordani; Meneses Sevilha Castro, Douglas Gomes; Becker, Jefferson; Bar-Or, Amit; Sato, Douglas Kazutoshi

Specific therapies targeting B lymphocytes in multiple sclerosis (MS) have demonstrated reductions in disease activity and disability progression. Several observational studies have also shown the effects of targeting B lymphocytes in other rare CNS inflammatory diseases, such as neuromyelitis optica spectrum disorder (NMOSD) and autoimmune encephalitis (AE). However, some drugs targeting cytokine receptors involved in B-lymphocyte maturation and proliferation resulted in negative outcomes in MS. These apparently conflicting findings have stimulated research on the pathophysiologic mechanisms of B lymphocytes in CNS inflammatory diseases. It has been demonstrated that B-lymphocytes participate in the pathogenesis of these conditions as antigen-presenting cells, producing proinflammatory cytokines that induce Th1 and Th17 responses and producing antibodies. However, they are also able to produce anti-inflammatory cytokines, such as interleukin (IL)-10, functioning as regulators of autoimmunity. Understanding these diverse effects is essential for the development of focused treatments. In this review, we discuss the possible mechanisms that underlie B lymphocyte involvement in MS, NMOSD, and AE, and the outcomes obtained by treatments targeting B lymphocytes.