Aberrant B Cell Selection and Activation in Systemic Lupus Erythematosus. (1st August 2013)

• Record Type: Journal Article
• Authors: Kil, Laurens P.; Hendriks, Rudi W.
• Is Part Of: International reviews of immunology. Volume 32:Number 4(2013:Aug.)
• Page Start: 445
• Page End: 470
• Publication Date: 2013-08-01
• Subjects: antibody secreting cells -- B cell activation -- B cell receptor signaling -- B cell tolerance -- B lymphocytes -- follicular helper T cells -- germinal centers -- systemic lupus erythematosus -- Toll-like receptors; Immunology -- Periodicals; Autoimmune diseases -- Periodicals; 616.079
• DOI: 10.3109/08830185.2013.786712
• Languages: English
• ISSNs: 0883-0185

Abstract

Abstract : 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.