The Journal of Experimental Medicine
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© The Rockefeller University Press, 0022-1007/1999/12/1697/ $5.00
The Journal of Experimental Medicine, Volume 190, Number 11, December 6, 1999 1697-1710

Original Article

Mice Transgenic for Baff Develop Lymphocytic Disorders along with Autoimmune Manifestations

Fabienne Mackaya, Stephen A. Woodcocka, Pornsri Lawtona, Christine Ambrosea, Manfred Baetscherb, Pascal Schneiderc, Jurg Tschoppc, and Jeffrey L. Browninga

a Department of Immunology, Inflammation and Cell Biology, Biogen, Cambridge, Massachusetts 02142
b Oregon Health Sciences University, Portland, Oregon 97201-9847
c Institute of Biochemistry, University of Lausanne, CH-1066 Epalinges, Switzerland
Biogen, 12 Cambridge Center, Cambridge, MA 02142.617-679-2304617-679-2161

fabienne_mackay{at}biogen.com

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.

Key Words: autoantibodies • tumor necrosis factor–related • B cell • rheumatoid factors • transgenic

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.

© 1999 The Rockefeller University Press


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