Aberrant B cell selection and activation in systemic lupus erythematosus

Int Rev Immunol. 2013 Aug;32(4):445-70. doi: 10.3109/08830185.2013.786712. Epub 2013 Jun 14.


The detrimental role of B lymphocytes in systemic lupus erythematosus (SLE) is evident from the high levels of pathogenic antinuclear autoantibodies (ANAs) found in SLE patients. Affirming this causative role, additional antibody-independent roles of B cells in SLE were appreciated. In recent years, many defects in B cell selection and activation have been identified in murine lupus models and SLE patients that explain the increased emergence and persistence of autoreactive B cells and their lowered activation threshold. Therefore, clinical trials with B cell depletion regimens in SLE patients were initiated but disappointingly the efficacy of B cell depleting agents proved to be limited. Remarkably however, a major breakthrough in SLE therapy was accomplished by blocking B cell survival factors rather then eliminating B cells. This surprising finding indicates that although SLE is a B cell-driven disease, the amplifying crosstalk between B cells and other cells of the immune system likely evokes the observed tolerance breakdown in B cells. Moreover, this implies that intelligent interception of pro-inflammatory loops rather then selectively silencing B cells will be key to the development of new SLE therapies. In this review, we will not only highlight the intrinsic B cell defects that facilitate the persistence of autoreactive B cells and their activation, but in addition we will focus on B cell extrinsic signals derived from T cells and innate immune cells that lower the activation threshold for B cells.

Publication types

  • Review

MeSH terms

  • Animals
  • Autoantibodies / immunology
  • Autoimmunity
  • B-Lymphocytes / immunology*
  • B-Lymphocytes / metabolism
  • Cell Communication / immunology
  • Clonal Selection, Antigen-Mediated / immunology*
  • Humans
  • Immune Tolerance
  • Immunity, Innate
  • Lupus Erythematosus, Systemic / immunology*
  • Lupus Erythematosus, Systemic / metabolism
  • Lymphocyte Activation / immunology*
  • Receptors, Antigen, B-Cell / metabolism
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism
  • Toll-Like Receptors / metabolism


  • Autoantibodies
  • Receptors, Antigen, B-Cell
  • Toll-Like Receptors