Are the B cells cast with the leading part in the Sjogren's syndrome scenario?

Abstract

The autoimmune exocrinopathy Sjögren's syndrome (SS) is characterized by mononuclear cell (MNC) infiltrates of exocrine glands and overactivity of B lymphocytes. Although T cells have long been perceived as the prime effectors, increasing evidence indicates that the key role is rather served by B cells. Among related abnormalities are rheumatoid factor (RF), anti-SSA/Ro, and anti-SSB/La antibodies (Ab). Also, supporting this view is our finding of an increase in the number of circulating naïve mature B (Bm) cells, with a reciprocal decrease in that of memory B cells. Furthermore, a ratio of Bm2-plus-Bm2' cells to early Bm5-plus-late Bm5 above 5 is diagnostic. This variation partly reflects the migration of active memory B cells into the exocrine glands of the patients, as well as into their skin. More recently, the B-cell-activating factor of the TNF family (BAFF) has been endorsed with a pivotal role in B-cell survival and hence implicated in the pathogenesis of autoimmunity. In practice, B cells have turned quite attractive as a target for biotherapy. For example, treatment with anti-CD20 Ab has afforded some benefits in this disease, while BAFF blockers are still on the way, but should expand our armamentarium for treating SS. With such B-cell-directed biotherapies in mind, we delineate herein the distinguishing traits of B lymphocytes in SS.