Checkpoints controlling the induction of B cell mediated autoimmunity in human autoimmune diseases

Eur J Immunol. 2020 Dec;50(12):1885-1894. doi: 10.1002/eji.202048820. Epub 2020 Dec 2.


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.

Keywords: autoimmunity; cross presentation/priming; regulatory T cells; rheumatology; tolerance.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Autoimmune Diseases / immunology*
  • Autoimmunity / immunology*
  • B-Lymphocytes / immunology*
  • Cross Reactions / immunology
  • Humans
  • Immune Tolerance / immunology