TNF deficiency fails to protect BAFF transgenic mice against autoimmunity and reveals a predisposition to B cell lymphoma.

Détails

ID Serval
serval:BIB_A47A8742F58F
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
TNF deficiency fails to protect BAFF transgenic mice against autoimmunity and reveals a predisposition to B cell lymphoma.
Périodique
Journal of Immunology
Auteur(s)
Batten M., Fletcher C., Ng L.G., Groom J., Wheway J., Laâbi Y., Xin X., Schneider P., Tschopp J., Mackay C.R., Mackay F.
ISSN
0022-1767 (Print)
ISSN-L
0022-1767
Statut éditorial
Publié
Date de publication
2004
Volume
172
Numéro
2
Pages
812-822
Langue
anglais
Résumé
TNF is well characterized as a mediator of inflammatory responses. TNF also facilitates organization of secondary lymphoid organs, particularly B cell follicles and germinal centers, a hallmark of T-dependent Ab responses. TNF also mediates defense against tumors. We examined the role of TNF in the development of inflammatory autoimmune disorders resembling systemic lupus erythematosus and Sjögren's syndrome induced by excess B cell-activating factor belonging to the TNF family (BAFF), by generating BAFF-transgenic (Tg) mice lacking TNF. TNF(-/-) BAFF-Tg mice resembled TNF(-/-) mice, in that they lacked B cell follicles, follicular dendritic cells, and germinal centers, and have impaired responses to T-dependent Ags. Nevertheless, TNF(-/-) BAFF-Tg mice developed autoimmune disorders similar to that of BAFF-Tg mice. Disease in TNF(-/-) BAFF-Tg mice correlates with the expansion of transitional type 2 and marginal zone B cell populations and enhanced T-independent immune responses. TNF deficiency in BAFF-Tg mice also led to a surprisingly high incidence of B cell lymphomas (>35%), which most likely resulted from the combined effects of BAFF promotion of neoplastic B cell survival, coupled with lack of protective antitumor defense by TNF. Thus, TNF appears to be dispensable for BAFF-mediated autoimmune disorders and may, in fact, counter any proneoplastic effects of high levels of BAFF in diseases such as Sjögren's syndrome, systemic lupus erythematosus, and rheumatoid arthritis.
Mots-clé
Animals, Antigens, T-Independent/physiology, Autoantibodies/biosynthesis, B-Cell Activating Factor, B-Lymphocyte Subsets/metabolism, B-Lymphocyte Subsets/pathology, CD4-Positive T-Lymphocytes/pathology, Genetic Predisposition to Disease, Glomerulonephritis/genetics, Glomerulonephritis/immunology, Lupus Erythematosus, Systemic/genetics, Lupus Erythematosus, Systemic/immunology, Lymphoma/genetics, Lymphoma/immunology, Lymphoma, B-Cell/genetics, Lymphoma, B-Cell/immunology, Membrane Proteins/genetics, Membrane Proteins/physiology, Mice, Mice, Inbred C57BL, Mice, Knockout, Mice, Transgenic, Sjogren's Syndrome/genetics, Sjogren's Syndrome/immunology, Splenomegaly/genetics, Splenomegaly/immunology, Tumor Necrosis Factor-alpha/deficiency, Tumor Necrosis Factor-alpha/genetics, Up-Regulation/genetics, Up-Regulation/immunology
Pubmed
Web of science
Création de la notice
24/01/2008 16:18
Dernière modification de la notice
20/08/2019 16:09
Données d'usage