Salivary gland lymphomas in patients with Sjogren's syndrome may frequently develop from rheumatoid factor B cells

Objective. Patients with Sjogren's syndrome (SS) have an increased risk of developing monoclonal B cell non-Hodgkin's lymphomas (MNHL), which frequent ly occur in the salivary glands (SG). The transition from the benign lympho cyte infiltrate of the gland that characterizes SS to MNHL is not well unde rstood. Previous sequence analyses of the expressed variable (V) region gen es have supported the theory that the surface Ig (sIg) plays an important r ole in the initial expansion of nonmalignant B cell clones and in lymphomag enesis. However, the antigenic specificities of these B cells were unknown. We describe the specificities of the Ig expressed by 2 cases of MNHL that developed in the SG of 2 patients with SS. Methods. The expressed V genes were amplified by polymerase chain reaction from biopsy specimens, sequenced, and subcloned into eukaryotic expression vectors. The constructs were transfected into P3X63-Ag8.653 cells to obtain 2 monoclonal cell lines, each secreting 1 of the sig expressed by the MNHL . These IgM were tested by enzyme-linked immunosorbent assay and immunofluo rescence against a panel of antigens potentially implicated in SS. Results. Our main finding was that the Ig products of the neoplastic B cell s were rheumatoid factors (RF). Contrary to expectations, they did not reac t with nuclear or cytoplasmic antigens, double-stranded DNA, self antigens commonly bound by natural autoantibodies, or SG tissue. Conclusion. Previous analyses of V gene use have provided indirect evidence that SC MNHL may frequently express RF. We demonstrate that this hypothesi s is true in the 2 patients we studied. Large-scale studies will be needed to establish. the exact frequency of RF specificity among SS-associated MNH L.