The BAFF/APRIL system: an important player in systemic rheumatic diseases

Curr Dir Autoimmun. 2005:8:243-65. doi: 10.1159/000082106.

Abstract

Many rheumatic diseases have an autoimmune basis, characterized by organ-specific inflammation and tissue destruction. Diseases such as rheumatoid arthritis, systemic lupus erythematosus or Sjögren's syndrome often associate with abnormal B cell function and the production of various autoantibodies. B cell activating factor belonging to the TNF family (BAFF) is a B cell survival factor essential for B cell maturation, but also contributes to autoimmunity when overexpressed in mice. In addition, elevated levels of BAFF have been detected in the serum of patients with various rheumatic diseases, suggesting a role for this factor in these pathologies. BAFF has additional functions that may be important in rheumatic diseases. For instance, excess BAFF leads to the expansion of a subset of B cells named marginal zone (MZ) B cells, a cell type able to activate naïve T cells. In addition, expansion of the MZ B cell population correlates with certain autoimmune diseases, and these cells have been detected in inflamed tissues in mice and humans. Recently, BAFF was shown to also stimulate T cell activation, an aspect that may also contribute to autoimmunity. Finally, BAFF has emerged as a potent survival factor for B cell lymphomas and as such may be involved in promoting B cell cancers. This result possibly offers an explanation for the occasional lymphoma complication observed in a subset of patients with certain rheumatic diseases, particularly Sjögren's syndrome. New elements about BAFF biology indicate that this factor may be involved in a wider range of pathologies than first anticipated, and inhibitors of this factor are likely to provide attractive new treatments for rheumatic diseases and B cell lymphomas.

Publication types

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

MeSH terms

  • Animals
  • Arthritis, Rheumatoid / immunology
  • Autoimmune Diseases / immunology
  • B-Cell Activating Factor
  • B-Cell Activation Factor Receptor
  • B-Lymphocytes / immunology
  • Humans
  • Leukemia, B-Cell / immunology
  • Ligands
  • Lymphoma, B-Cell / immunology
  • Membrane Proteins / immunology*
  • Mice
  • Models, Immunological
  • Neoplasms, Experimental / immunology
  • Receptors, Tumor Necrosis Factor / immunology
  • Rheumatic Diseases / etiology
  • Rheumatic Diseases / immunology*
  • Rheumatic Diseases / therapy
  • Sjogren's Syndrome / immunology
  • Tumor Necrosis Factor Ligand Superfamily Member 13
  • Tumor Necrosis Factor-alpha / immunology*

Substances

  • B-Cell Activating Factor
  • B-Cell Activation Factor Receptor
  • Ligands
  • Membrane Proteins
  • Receptors, Tumor Necrosis Factor
  • TNFRSF13C protein, human
  • TNFSF13 protein, human
  • TNFSF13B protein, human
  • Tnfrsf13c protein, mouse
  • Tnfsf13 protein, mouse
  • Tnfsf13b protein, mouse
  • Tumor Necrosis Factor Ligand Superfamily Member 13
  • Tumor Necrosis Factor-alpha