B cell depletion therapies in autoimmune disease: advances and mechanistic insights

• Published in: Nature reviews. Drug discovery Vol. 20; no. 3; pp. 179 - 199
• Main Authors: Lee, Dennis S. W., Rojas, Olga L., Gommerman, Jennifer L.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.03.2021; Nature Publishing Group
• Subjects: 631/250/2152; 631/250/38; 692/308/153; Animals; Antibodies; Antigens; Arthritis; Autoimmune diseases; Autoimmune Diseases - immunology; B cells; B-Lymphocytes - immunology; Biomedical and Life Sciences; Biomedicine; Biotechnology; Cancer Research; Care and treatment; Cell adhesion & migration; Cellular therapy; Clinical Trials as Topic; Control; Dendritic cells; Encephalomyelitis; Forecasts and trends; Humans; Lupus; Lymphocyte Depletion - methods; Malaria; Medicinal Chemistry; Methods; Molecular Medicine; Multiple sclerosis; Pharmacology/Toxicology; Review; Review Article; Canada
• ISSN: 1474-1776; 1474-1784
• DOI: 10.1038/s41573-020-00092-2

In the past 15 years, B cells have been rediscovered to be not merely bystanders but rather active participants in autoimmune aetiology. This has been fuelled in part by the clinical success of B cell depletion therapies (BCDTs). Originally conceived as a method of eliminating cancerous B cells, BCDTs such as those targeting CD20, CD19 and BAFF are now used to treat autoimmune diseases, including systemic lupus erythematosus and multiple sclerosis. The use of BCDTs in autoimmune disease has led to some surprises. For example, although antibody-secreting plasma cells are thought to have a negative pathogenic role in autoimmune disease, BCDT, even when it controls the disease, has limited impact on these cells and on antibody levels. In this Review, we update our understanding of B cell biology, review the results of clinical trials using BCDT in autoimmune indications, discuss hypotheses for the mechanism of action of BCDT and speculate on evolving strategies for targeting B cells beyond depletion. Examining B cell depletion therapy (BCDT), an approved treatment for B cell malignancies, in autoimmune conditions has provided key insights into basic B cell biology. In this Review, Gommerman and colleagues discuss BCDT in autoimmune conditions, highlighting diseases in which BCDT has been clinically effective and the potential and pitfalls for BCDT in autoimmune conditions in which it has not yet been efficacious.