B-cell tolerance breakdown in Sjögren's syndrome: focus on BAFF

Autoimmun Rev. 2010 Jul;9(9):604-8. doi: 10.1016/j.autrev.2010.05.006. Epub 2010 May 8.


Sjögren's syndrome (SS) is an autoimmune epithelitis hallmarked by a destruction of epithelial cells, the subsequent lymphocytic infiltration of exocrine glands and their ensuing dryness. Given the prominent role currently assigned to B cells in SS, it is not surprising that the B cell activating factor belonging to the Tumor Necrosis Factor family (BAFF) is involved in its pathogenesis. When overexpressed, this cytokine leads to self-reactive B cells emergence at the transitional B-cell stage. BAFF overexpression that has been observed in SS, is associated with B-cell tolerance breakdown and autoantibody production. Furthermore, BAFF is responsible for the abnormal distribution of B cells subsets and B-cell hyperactivity described in the blood. In the salivary glands, a minority of B-cell clusters represent ectopic germinal center cells, while the majority manifest features consistent with transitional type 2 (T2) and marginal-zone (MZ)-like B cells. Interestingly, both types of B-cell cluster include autoreactive B cells and BAFF is associated with expansion of T2 B cells and MZ-like B cells in the salivary glands. Finally, BAFF plays a major role in B-cell repopulation after their depletion by rituximab in SS.

Publication types

  • Review

MeSH terms

  • Animals
  • Autoantibodies / metabolism
  • B-Cell Activating Factor / genetics
  • B-Cell Activating Factor / immunology*
  • B-Lymphocytes / immunology*
  • B-Lymphocytes / metabolism
  • B-Lymphocytes / pathology*
  • Germinal Center / immunology
  • Germinal Center / metabolism
  • Germinal Center / pathology
  • Humans
  • Immune Tolerance*
  • Mice
  • Mice, Transgenic
  • Precursor Cells, B-Lymphoid
  • Salivary Glands / immunology
  • Salivary Glands / metabolism
  • Salivary Glands / pathology
  • Sjogren's Syndrome / etiology
  • Sjogren's Syndrome / immunology*
  • Sjogren's Syndrome / pathology*


  • Autoantibodies
  • B-Cell Activating Factor