Mice Transgenic for BAFF Develop Lymphocytic Disorders Along with Autoimmune Manifestations

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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 Mackay^a, Stephen A. Woodcock^a, Pornsri Lawton^a, Christine Ambrose^a, Manfred Baetscher^b, Pascal Schneider^c, Jurg Tschopp^c, and Jeffrey L. Browning^a
^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

Correspondence to: Fabienne Mackay, Biogen, 12 Cambridge Center, Cambridge, MA 02142. Tel:617-679-2161 Fax:617-679-2304 E-mail: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 costimulatestheir growth in vitro. Mice transgenic for BAFF have vastlyincreased numbers of mature B and effector T cells, and developautoimmune-like manifestations such as the presence of highlevels of rheumatoid factors, circulating immune complexes,anti–DNA autoantibodies, and immunoglobulin depositionin the kidneys. This phenotype is reminiscent of certain humanautoimmune disorders and suggests that dysregulation of BAFFexpression may be a critical element in the chain of eventsleading to autoimmunity.

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

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