B cells in multiple sclerosis therapy-A comprehensive review

Abstract

For decades, B cells were ignored in multiple sclerosis (MS) pathogenesis, and the disease was always regarded as a T cell-mediated disorder. Recent evidence shows that there is an antigen-driven B-cell response in the central nervous system of patients with MS, and memory B cells/plasma cells are detectable in MS lesions. The striking efficacy of B cell-depleting therapies in reducing the inflammatory activity of the disease highlights that B cells may play more pathogenetic roles than expected. B cells express several unique characteristic markers on their surface, for example, CD19, CD20 molecules, that provide selective targets for monoclonal antibodies. In this respect, several B cell-targeted therapies emerged, including anti-CD20 antibodies (rituximab, ocrelizumab, and ofatumumab), anti-CD19 antibody (inebilizumab), and agents targeting the BAFF/APRIL signaling pathway (atacicept, belimumab, and LY2127399). In this review, we discuss, in detail, the immunobiology of B cells and their protective and destructive roles in MS pathogenesis. In the second part, we list the completed and ongoing clinical trials investigating the safety and efficacy of B cell-related monoclonal antibodies in MS.

Biological characteristics of transcription factor RelB in different immune cell types: implications for the treatment of multiple sclerosis

“…For decades, MS was generally known as a mainly T cell-mediated disease, and the role of B cells in MS was overlooked; however, a growing amount of evidence shows the significant involvement of B cells in MS pathology [181,182]. When naïve B cells encounter myelin antigens, they are activated and differentiate into plasma cells, memory B cells and regulatory B cells (Bregs) with the help of follicular helper T (Tfh) cells [108].…”

Effects of Treatment with the Hypomethylating Agent 5-aza-2′-deoxycytidine in Murine Type II Collagen-Induced Arthritis

“…So far, to the best of our knowledge, no data is available in the literature on the effects of DAC on B cell function, and we are currently prioritizing this area of research. This is also of particular relevance as B cells are being recognized as important effector cells in autoimmune diseases, such as RA and MS. As discussed above, certain forms of both diseases benefit from the therapeutic use of biological drugs targeting, specifically, B cell number and function, such as rituximab and ocrelizumab [12,30].…”

Association of BAFF gene polymorphisms with multiple sclerosis progression

“…Следует отметить, что в настоящее время с учетом патогенетической значимости BAFF и его гомолога APRIL (А proliferation-inducing ligand) при ряде аутоиммунных заболеваний были созданы и применяются на практике несколько препаратов, ингибирующих эффекты этих цитокинов: анти-BAFF гуманизированные моноклональные антитела (Belimumab и LY2127399), растворимый рецептор TACI, который связывает цитокины BAFF и APRIL (soluble decoy TACI-Fc fusion protein, Аtacicept) и др. [6].…”

“…Относительно недавно идентифицирован один из таких цитокинов, принадлежащих к семейству фактора некроза опухоли (ФНО-семейство) -фактор активации B-клеток (B-cell activating factor, BAFF; B Lymphocyte Stimulator, BLyS; tumor necrosis factor ligand superfamily member 13, TNFSF13B). Являясь мощным костимулятором В-клеток, BAFF способствует дифференцировке, пролиферации и выживаемости этих клеток, участвующих в иммунопатологических процессах при РС [5,6].…”

“…Многие годы РС рассматривали как заболевание, опосредованное преимущественно Т-клетками. В последние десятилетия установлена важная роль В-клеток в развитии и прогрессировании РС посредством антигенпрезентации и продукции множества цитокинов [6,16,17]. Поэтому все большее внимание уделяется изучению закономерностей функционирования В-клеточного звена иммунитета при РС в связи не только с антителообразованием, но и с участием в антигенпрезентации и продукции множества цитокинов.…”