Bm1-Bm5 classification of peripheral blood B cells reveals circulating germinal center founder cells in healthy individuals and disturbance in the B cell subpopulations in patients with primary Sjogren's syndrome

Analyses of B cells in the bone marrow and secondary lymphoid tissues have revealed a broad range of cell surface markers defining B cell subpopulatio ns, but only a few of these have been used to analyze B cell subpopulations in peripheral blood (PB). We report here the delineation of circulating PB B cell subpopulations by staining for CD19, CD38, and IgD in combination w ith CD10, CD44, CD77, CD95, CD23, IgM, and the B cell memory marker CD27. T he utility of this approach is shown by the demonstration of disturbances o f circulating B cell subpopulations in patients with autoimmune disease. Fi ve mature B cell (Bm) subpopulations were identified in normal PB that were comparable with the tonsillar Bm1, Bm2, early Bm5, Bm5 subpopulations and, surprisingly, to the germinal center (GC) founder cell subpopulation (Bm2' and Bm3 delta -4 delta), suggesting that some GC founder cells are circula ting. No PB B cells resembled the Bm3 and Bm4 GC cells. Remarkably, some ce lls with the CD38(-)IgD(+) phenotype, previously known as naive Bm1 cells, expressed CD27. The CD38(-)IgD(+) subpopulation therefore includes both nai ve Bmi cells and lgD(+) memory B cells. This new classification of B cell d evelopmental stages reveals disturbances in the proportions of B cell subpo pulations in primary Sjogren's syndrome (pSS) patients compared with health y donors and rheumatoid arthritis patients. Patients with pSS contained a s ignificantly higher percentage of B cells in two activated stages, which mi ght reflect a disturbance in B cell trafficking and/or alteration in B cell differentiation. These findings could be of diagnostic significance for pS S.