| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
* Department of Medicine,
Division of Gastrointestinal and Liver Diseases and
Division of Rheumatology,
Department of Pathology, University of Southern California Keck School of Medicine, Los Angeles, CA 90033;
¶ Department of Medicine, Hospital for Special Surgery, Weill Medical College of Cornell University, New York, NY 10021;
|| Division of Rheumatology, Albert Einstein College of Medicine, Bronx, NY 10461; and
# Research Department, Biogen Idec, Cambridge, MA 02142
Constitutive overexpression of B cell-activating factor belonging to the TNF family (BAFF) promotes development of systemic lupus erythematosus (SLE), and treatment of SLE mice with BAFF antagonists ameliorates disease. To determine whether SLE can develop de novo in BAFF-deficient hosts, BAFF-deficient New Zealand Mixed (NZM) 2328 (NZM.Baff–/–) mice were generated. In NZM.Baff–/– mice, spleen B cells (including CD5+ B1a and CD5– B1b B cells), germinal centers, Ig-secreting cells, and T cells were reduced in comparison to NZM.Baff+/+ mice. Serum total Ig and autoantibody levels were reduced at 4–6 mo but approached wild-type levels with increasing age, indicating that autoreactive B cells can survive and secrete autoantibodies despite the complete absence of BAFF. At least some of these autoantibodies are nephrophilic in that glomerular deposition of total IgG and IgG1 (but not of IgG2a, IgG2b, or C3) was substantial in NZM.Baff–/– mice by 12–13 mo of age. Despite proliferative glomerulonephritis, highlighted by widespread glomerular hyaline thrombi, being common among NZM.Baff–/– mice by 6–7 mo of age, severe proteinuria and mortality were greatly attenuated. These results demonstrate that the lifelong absence of BAFF does not protect NZM 2328 mice from serological autoimmunity and renal pathology. Nevertheless, the character of the renal pathology is altered, and the mice are largely spared from clinically overt disease (severe proteinuria and premature death). These observations may have profound ramifications for the use of BAFF antagonists in human SLE and related diseases.
This article has been cited by other articles:
|
|
 |
|
  X. Li, K. Su, C. Ji, A. J. Szalai, J. Wu, Y. Zhang, T. Zhou, R. P. Kimberly, and J. C. Edberg Immune Opsonins Modulate BLyS/BAFF Release in a Receptor-Specific Fashion J. Immunol., July 15, 2008; 181(2): 1012 - 1018. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Stohl, N. Jacob, W. J. Quinn III, M. P. Cancro, H. Gao, C. Putterman, X. Gao, L. Pricop, and M. N. Koss Global T Cell Dysregulation in Non-Autoimmune-Prone Mice Promotes Rapid Development of BAFF-Independent, Systemic Lupus Erythematosus-Like Autoimmunity J. Immunol., July 1, 2008; 181(1): 833 - 841. [Abstract] [Full Text] [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]
|
|
|
|
 |
|
 D. A. Isenberg, J. J. Manson, M. R. Ehrenstein, and A. Rahman Fifty years of anti-ds DNA antibodies: are we approaching journey's end? Rheumatology, July 1, 2007; 46(7): 1052 - 1056. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
