The percentage of CD27(+) B cells in peripheral blood (PB) of patients with primary Sjögren's syndrome (pSS) is significantly decreased compared to normals. In contrast, serum levels of the soluble form of CD27 (sCD27) are significantly higher in pSS patients, with a strong positive correlation between sCD27 and serum IgG levels. In vitro experiments demonstrate that normal B cells cultured under conditions driving plasma cell differentiation result in the production of substantial amounts of sCD27. Analyses of V(H)-region genes from sorted CD27(+) and CD27(-) B cells from pSS patients confirm that the CD27(+) population corresponds to the somatically mutated memory compartment, as in healthy individuals. Together our data indicate that in pSS, there is an abnormal differentiation of B cells to plasma cells resulting in a depression of the circulating memory B-cell pool and the release of significant amounts of sCD27 and IgG.