B-cell tolerance breakdown in Sjögren's syndrome: focus on BAFF.
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.
Varin
Marie-Michèle
MM
EA 2216 Immunologie et Pathologie, Université de Brest, France.
Le Pottier
Laëtitia
L
Youinou
Pierre
P
Saulep
Damien
D
Mackay
Fabienne
F
Pers
Jacques-Olivier
JO
D000818:Animals; D001323:Autoantibodies / Q000378:metabolism; D053264:B-Cell Activating Factor / Q000235:genetics / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D018858:Germinal Center / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007108:Immune Tolerance; D051379:Mice; D008822:Mice, Transgenic; D054448:Precursor Cells, B-Lymphoid; D012469:Salivary Glands / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D012859:Sjogren's Syndrome / Q000209:etiology / Q000276:immunology* / Q000473:pathology*
D001323:Autoantibodies; D053264:B-Cell Activating Factor