Checkpoints controlling the induction of B cell mediated autoimmunity in human autoimmune diseases. Issue 12 (2nd December 2020)

• Record Type: Journal Article
• Authors: Reijm, S.; Kissel, T.; Toes, R.E.M.
• Is Part Of: European journal of immunology. Volume 50:Issue 12(2020)
• Page Start: 1885
• Page End: 1894
• Publication Date: 2020-12-02
• Subjects: autoimmunity -- cross presentation/priming -- regulatory T cells -- rheumatology -- tolerance; Immunology -- Periodicals; 616.079
• DOI: 10.1002/eji.202048820
• Languages: English
• ISSNs: 0014-2980

Abstract

Abstract: B cell targeting therapies are effective in various autoimmune diseases, among others rheumatoid arthritis, pemphigus vulgaris, and systemic lupus erythematosus. Given these successes, it is evident that B cells are central orchestrators in the processes leading to the signs and symptoms hallmarking many human autoimmune diseases. The pathways provoking the generation of such autoreactive B cells or mechanisms preventing their induction in health are, however, poorly explored. Nevertheless, such information is crucial for the development of preventative/curative interventions aiming to permanently deplete‐ or prohibit the emergence of autoreactive B cells. Hence, this review will focus on how B cell tolerance might be breached, and which checkpoints are at play preventing the arousal of autoreactive B cells in human. Especially antigen presentation by follicular dendritic cells, somatic hypermutation, and cross‐reactivity to the microbiome/environment could operate as actors playing pivotal roles in the induction of B cell‐mediated humoral autoimmunity. Moreover, we highlight the human autoimmune disease rheumatoid arthritis as a prototype where autoreactive B cells combine several mechanisms to overcome peripheral B cell checkpoints. Abstract : Follicular dendritic cells present antigen and provide co‐stimulation to the B cell (1). Activated B cells undergo somatic hypermutation, leading potentially to self‐antigen recognition or they show cross‐reactivity (2). The cross‐/ auto‐reactive B cell can recruit T cell help from pathogen‐specific T cells (3) and induces autoimmune disease (4).