The cause of many autoimmune and inflammatory diseases is unresolved, although dysregulated production of tumor necrosis factor (TNF) family members appears to be important in many cases. BAFF, a new member of the TNF family, binds to B cells and costimulates their growth in vitro. Mice transgenic for BAFF have vastly increased numbers of mature B and effector T cells, and develop autoimmune-like manifestations such as the presence of high levels of rheumatoid factors, circulating immune complexes, anti–DNA autoantibodies, and immunoglobulin deposition in the kidneys. This phenotype is reminiscent of certain human autoimmune disorders and suggests that dysregulation of BAFF expression may be a critical element in the chain of events leading to autoimmunity.
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6 December 1999
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December 06 1999
Mice Transgenic for Baff Develop Lymphocytic Disorders along with Autoimmune Manifestations
Fabienne Mackay,
Fabienne Mackay
aDepartment of Immunology, Inflammation and Cell Biology, Biogen, Cambridge, Massachusetts 02142
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Stephen A. Woodcock,
Stephen A. Woodcock
aDepartment of Immunology, Inflammation and Cell Biology, Biogen, Cambridge, Massachusetts 02142
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Pornsri Lawton,
Pornsri Lawton
aDepartment of Immunology, Inflammation and Cell Biology, Biogen, Cambridge, Massachusetts 02142
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Christine Ambrose,
Christine Ambrose
aDepartment of Immunology, Inflammation and Cell Biology, Biogen, Cambridge, Massachusetts 02142
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Manfred Baetscher,
Manfred Baetscher
bOregon Health Sciences University, Portland, Oregon 97201-9847
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Pascal Schneider,
Pascal Schneider
cInstitute of Biochemistry, University of Lausanne, CH-1066 Epalinges, Switzerland
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Jurg Tschopp,
Jurg Tschopp
cInstitute of Biochemistry, University of Lausanne, CH-1066 Epalinges, Switzerland
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Jeffrey L. Browning
Jeffrey L. Browning
aDepartment of Immunology, Inflammation and Cell Biology, Biogen, Cambridge, Massachusetts 02142
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Fabienne Mackay
aDepartment of Immunology, Inflammation and Cell Biology, Biogen, Cambridge, Massachusetts 02142
Stephen A. Woodcock
aDepartment of Immunology, Inflammation and Cell Biology, Biogen, Cambridge, Massachusetts 02142
Pornsri Lawton
aDepartment of Immunology, Inflammation and Cell Biology, Biogen, Cambridge, Massachusetts 02142
Christine Ambrose
aDepartment of Immunology, Inflammation and Cell Biology, Biogen, Cambridge, Massachusetts 02142
Manfred Baetscher
bOregon Health Sciences University, Portland, Oregon 97201-9847
Pascal Schneider
cInstitute of Biochemistry, University of Lausanne, CH-1066 Epalinges, Switzerland
Jurg Tschopp
cInstitute of Biochemistry, University of Lausanne, CH-1066 Epalinges, Switzerland
Jeffrey L. Browning
aDepartment of Immunology, Inflammation and Cell Biology, Biogen, Cambridge, Massachusetts 02142
Abbreviations used in this paper: AP, alkaline phosphatase; BAFF, B cell activating factor belonging to the TNF family; BM, bone marrow; BrdU, 5-bromo-2′-deoxyuridine; CIC, circulating immune complexes; ds, double stranded; HRP, horseradish peroxidase; MLN, mesenteric lymph node; MZ, marginal zone; ss, single stranded; Tg, transgenic.
Received:
August 10 1999
Revision Requested:
September 30 1999
Accepted:
October 01 1999
Online ISSN: 1540-9538
Print ISSN: 0022-1007
© 1999 The Rockefeller University Press
1999
The Rockefeller University Press
J Exp Med (1999) 190 (11): 1697–1710.
Article history
Received:
August 10 1999
Revision Requested:
September 30 1999
Accepted:
October 01 1999
Citation
Fabienne Mackay, Stephen A. Woodcock, Pornsri Lawton, Christine Ambrose, Manfred Baetscher, Pascal Schneider, Jurg Tschopp, Jeffrey L. Browning; Mice Transgenic for Baff Develop Lymphocytic Disorders along with Autoimmune Manifestations. J Exp Med 6 December 1999; 190 (11): 1697–1710. doi: https://doi.org/10.1084/jem.190.11.1697
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