TNF Deficiency Fails to Protect BAFF Transgenic Mice against Autoimmunity and Reveals a Predisposition to B Cell Lymphoma

摘要: TNF is well characterized as a mediator of inflammatory responses. also facilitates organization secondary lymphoid organs, particularly B cell follicles and germinal centers, hallmark T-dependent Ab mediates defense against tumors. We examined the role in development autoimmune disorders resembling systemic lupus erythematosus Sjogren's syndrome induced by excess cell-activating factor belonging to family (BAFF), generating BAFF-transgenic (Tg) mice lacking TNF. TNF(-/-) BAFF-Tg resembled mice, that they lacked follicles, follicular dendritic cells, have impaired responses Ags. Nevertheless, developed similar mice. Disease correlates with expansion transitional type 2 marginal zone populations enhanced T-independent immune deficiency led surprisingly high incidence lymphomas (>35%), which most likely resulted from combined effects BAFF promotion neoplastic survival, coupled lack protective antitumor Thus, appears be dispensable for BAFF-mediated may, fact, counter any proneoplastic levels diseases such syndrome, erythematosus, rheumatoid arthritis.