Lymphoproliferative disease in SCID mice reconstituted with human Sjögren's syndrome lymphocytes

Patients with Sjögren's syndrome (SS) have increased frequency of non-Hodgkin's B-cell lymphoma. These lymphomas frequently use a specific subclass of kappa light chain (encoded by variable region gene segment Hum KV325) and exhibit bcl-2 protooncogene translocation t(14;18). In order to determine whether expansion of this B-cell subset could be reproduced in an animal model, immunodeficient SCID (CB-17) mice were reconstituted with lymphocytes from 4 different SS patients at high risk of the development of lymphoma. Tumor-like nodules developed in all 11 SCID mice that received at least 5 x 10(5) lymphocytes from SS salivary glands or peripheral blood samples. However, the tumor-like nodules in the SCID mice differed from SS lymphomas in vivo in that they (1) exhibited multiple immunoglobulin gene rearrangements; (2) did not have expansion of B-cells expressing the Hum KV325 K-light chain; and (3) lacked detectable t(14;18) translocations. Characterization of the SCID tumor-like nodules revealed a high level of Epstein-Barr virus (EBV) DNA, EBV-associated antigens (EA-R, EBNA-2, AND LMP), and the EBV-encoded cytokine BCRF-1 that is structurally similar to IL-10. These results demonstrate that the lymphoproliferation occurring in the salivary glands of SS patients is not reproduced in the SCID/hu chimeric mouse. It is likely that specific factors in the human salivary gland are required for development of lymphoma in SS patients and that such factors are not present in the SCID/hu chimeric mouse. Furthermore, EBV-induced lymphoproliferation, as seen in the SCID/hu chimera, does not lead to expansion of the same lymphoid subsets that occurs in vivo.