| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
* Department of Arthritis and Inflammation, Garvan Institute of Medical Research, Darlinghurst, New South Wales, Australia;
Department of Immunology, Laboratory of Lymphocyte Development, Pasteur Institute, Paris, France;
Institute of Biochemistry, University of Lausanne, Epalinges, Switzerland; and
Cooperative Research Center for Asthma, Sydney, Australia
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.
This article has been cited by other articles:
|
|
 |
|
  S.-H. Kuo, P.-Y. Yeh, L.-T. Chen, M.-S. Wu, C.-W. Lin, K.-H. Yeh, Y.-S. Tzeng, J.-Y. Chen, P.-N. Hsu, J.-T. Lin, et al. Overexpression of B cell-activating factor of TNF family (BAFF) is associated with Helicobacter pylori-independent growth of gastric diffuse large B-cell lymphoma with histologic evidence of MALT lymphoma Blood, October 1, 2008; 112(7): 2927 - 2934. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. E. Doyle, L. Boggs, R. Attia, L. R. Cooper, D. R. Saban, C. Q. Nguyen, and A. B. Peck Autoimmune Dacryoadenitis of NOD/LtJ Mice and Its Subsequent Effects on Tear Protein Composition Am. J. Pathol., October 1, 2007; 171(4): 1224 - 1236. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Binard and P. Youinou BAFF, A newcomer to the lupus party Lupus, September 1, 2007; 16(9): 699 - 700. [PDF]
|
|
|
|
 |
|
 J. R. Groom, C. A. Fletcher, S. N. Walters, S. T. Grey, S. V. Watt, M. J. Sweet, M. J. Smyth, C. R. Mackay, and F. Mackay BAFF and MyD88 signals promote a lupuslike disease independent of T cells J. Exp. Med., August 6, 2007; 204(8): 1959 - 1971. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Lavie, C. Miceli-Richard, M. Ittah, J. Sellam, J.-E. Gottenberg, and X. Mariette Increase of B cell-activating factor of the TNF family (BAFF) after rituximab treatment: insights into a new regulating system of BAFF production Ann Rheum Dis, May 1, 2007; 66(5): 700 - 702. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. M. Mills, G. Bonizzi, M. Karin, and R. C. Rickert Regulation of late B cell differentiation by intrinsic IKK{alpha}-dependent signals PNAS, April 10, 2007; 104(15): 6359 - 6364. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. P. Purdue, Q. Lan, A. Kricker, A. E. Grulich, C. M. Vajdic, J. Turner, D. Whitby, S. Chanock, N. Rothman, and B. K. Armstrong Polymorphisms in immune function genes and risk of non-Hodgkin lymphoma: findings from the New South Wales non-Hodgkin Lymphoma Study Carcinogenesis, March 1, 2007; 28(3): 704 - 712. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Chiu, W. Xu, B. He, S. R. Dillon, J. A. Gross, E. Sievers, X. Qiao, P. Santini, E. Hyjek, J.-w. Lee, et al. Hodgkin lymphoma cells express TACI and BCMA receptors and generate survival and proliferation signals in response to BAFF and APRIL Blood, January 15, 2007; 109(2): 729 - 739. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Schwaller, P. Schneider, P. Mhawech-Fauceglia, T. McKee, S. Myit, T. Matthes, J. Tschopp, O. Donze, F.-A. Le Gal, and B. Huard Neutrophil-derived APRIL concentrated in tumor lesions by proteoglycans correlates with human B-cell lymphoma aggressiveness Blood, January 1, 2007; 109(1): 331 - 338. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Mhawech-Fauceglia, G. Kaya, G. Sauter, T. McKee, O. Donze, J. Schwaller, and B. Huard The source of APRIL up-regulation in human solid tumor lesions J. Leukoc. Biol., October 1, 2006; 80(4): 697 - 704. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Hassler, C. Ramsey, M. C. Karlsson, D. Larsson, B. Herrmann, B. Rozell, M. Backheden, L. Peltonen, O. Kampe, and O. Winqvist Aire-deficient mice develop hematopoetic irregularities and marginal zone B-cell lymphoma Blood, September 15, 2006; 108(6): 1941 - 1948. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. P. Miller, J. E. Stadanlick, and M. P. Cancro Space, Selection, and Surveillance: Setting Boundaries with BLyS. J. Immunol., June 1, 2006; 176(11): 6405 - 6410. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Fu, Y.-C. Lin-Lee, L. V. Pham, A. Tamayo, L. Yoshimura, and R. J. Ford Constitutive NF-{kappa}B and NFAT activation leads to stimulation of the BLyS survival pathway in aggressive B-cell lymphomas Blood, June 1, 2006; 107(11): 4540 - 4548. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Wheway, C. R. Mackay, R. A. Newton, A. Sainsbury, D. Boey, H. Herzog, and F. Mackay A fundamental bimodal role for neuropeptide Y1 receptor in the immune system J. Exp. Med., December 5, 2005; 202(11): 1527 - 1538. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Bredberg, G. Henriksson, A. Larsson, R. Manthorpe, and A. Sallmyr Sjogren's syndrome and the danger model Rheumatology, August 1, 2005; 44(8): 965 - 970. [Full Text] [PDF]
|
|
|
|
|
|
M. Krumbholz, D. Theil, T. Derfuss, A. Rosenwald, F. Schrader, C.-M. Monoranu, S. L. Kalled, D. M. Hess, B. Serafini, F. Aloisi, et al. BAFF is produced by astrocytes and up-regulated in multiple sclerosis lesions and primary central nervous system lymphoma J. Exp. Med., January 18, 2005; 201(2): 195 - 200. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. J. Novak, D. M. Grote, M. Stenson, S. C. Ziesmer, T. E. Witzig, T. M. Habermann, B. Harder, K. M. Ristow, R. J. Bram, D. F. Jelinek, et al. Expression of BLyS and its receptors in B-cell non-Hodgkin lymphoma: correlation with disease activity and patient outcome Blood, October 15, 2004; 104(8): 2247 - 2253. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. G. Ng, A. P. R. Sutherland, R. Newton, F. Qian, T. G. Cachero, M. L. Scott, J. S. Thompson, J. Wheway, T. Chtanova, J. Groom, et al. B Cell-Activating Factor Belonging to the TNF Family (BAFF)-R Is the Principal BAFF Receptor Facilitating BAFF Costimulation of Circulating T and B Cells J. Immunol., July 15, 2004; 173(2): 807 - 817. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Robin Goodfellow (43-4) Rheumatology, April 1, 2004; 43(4): 540 - 540. [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
