The regulation of autoreactive B cells during innate immune responses.
Systemic lupus erythematosus (SLE) highlights the dangers of dysregulated B cells and the importance of initiating and maintaining tolerance. In addition to central deletion, receptor editing, peripheral deletion, receptor revision, anergy, and indifference, we have described a new mechanism of B cell tolerance wherein dendritic cells (DCs) and macrophages (MPhis) regulate autoreactive B cells during innate immune responses. In part, DCs and MPhis repress autoreactive B cells by releasing IL-6 and soluble CD40L (sCD40L). This mechanism is selective in that IL-6 and sCD40L do not affect Ig secretion by naïve cells during innate immune responses, allowing immunity in the absence of autoimmunity. In lupus-prone mice, DCs and MPhis are defective in secretion of IL-6 and sCD40L and cannot effectively repress autoantibody secretion suggesting that defects in DC/MPhi-mediated tolerance may contribute to the autoimmune phenotype. Further, these studies suggest that reconstituting DCs and MPhis in SLE patients might restore regulation of autoreactive B cells and provide an alternative to immunosuppressive therapies.
Vilen
Barbara J
BJ
Department of Microbiology, University of North Carolina, CB 7290, Chapel Hill, NC 27599, USA. barb_vilen@med.unc.edu
Rutan
Jennifer A
JA
D000818:Animals; D001323:Autoantibodies / Q000276:immunology / Q000378:metabolism; D001324:Autoantigens / Q000276:immunology / Q000378:metabolism; D015551:Autoimmunity / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D023201:CD40 Ligand / Q000276:immunology / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology*; D015850:Interleukin-6 / Q000276:immunology / Q000378:metabolism; D008180:Lupus Erythematosus, Systemic / Q000276:immunology* / Q000378:metabolism; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism; D055517:snRNP Core Proteins / Q000276:immunology / Q000378:metabolism
D001323:Autoantibodies; D001324:Autoantigens; D015850:Interleukin-6; D055517:snRNP Core Proteins; D023201:CD40 Ligand