Altered B cell signalling in autoimmunity

Nat Rev Immunol. 2017 Jul;17(7):421-436. doi: 10.1038/nri.2017.24. Epub 2017 Apr 10.


Recent work has provided new insights into how altered B cell-intrinsic signals - through the B cell receptor (BCR) and key co-receptors - function together to promote the pathogenesis of autoimmunity. These combined signals affect B cells at two distinct stages: first, in the selection of the naive repertoire; and second, during extrafollicular or germinal centre activation responses. Thus, dysregulated signalling can lead to both an altered naive BCR repertoire and the generation of autoantibody-producing B cells. Strikingly, high-affinity autoantibodies predate and predict disease in several autoimmune disorders, including type 1 diabetes and systemic lupus erythematosus. This Review summarizes how, rather than being a downstream consequence of autoreactive T cell activation, dysregulated B cell signalling can function as a primary driver of many human autoimmune diseases.

Publication types

  • Review

MeSH terms

  • Animals
  • Autoimmunity*
  • B-Lymphocytes / immunology*
  • B-Lymphocytes / metabolism
  • Humans
  • Receptors, Antigen, B-Cell / metabolism
  • Signal Transduction


  • Receptors, Antigen, B-Cell