The Journal of Experimental Medicine
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Published online 6 March 2000.
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© The Rockefeller University Press, 0022-1007/2000/3/883/ $5.00
The Journal of Experimental Medicine, Volume 191, Number 5, March 6, 2000 883-890

Original Article

Cd5 Maintains Tolerance in Anergic B Cells

Keli L. Hippena, Lina E. Tzea, and Timothy W. Behrensa

a Center for Immunology, Department of Medicine, University of Minnesota Medical School, Minneapolis, Minnesota 55455
[same address].612-625-2199612-625-5168

keli.l.hippen-1{at}tc.umn.edu

Clonal anergy of autoreactive B cells is a key mechanism regulating tolerance. Here, we show that anergic B cells express significant surface levels of CD5, a molecule normally found on T cells and a subset of B-1 cells. Breeding of the hen egg lysozyme (HEL) transgenic model for B cell anergy onto the CD5 null background resulted in a spontaneous loss of B cell tolerance in vivo. Evidence for this included elevated levels of anti-HEL immunoglobulin M (IgM) antibodies in the serum of CD5–/– mice transgenic for both an HEL-specific B cell receptor (BCR) and soluble lysozyme. "Anergic" B cells lacking CD5 also showed enhanced proliferative responses in vitro and elevated intracellular Ca2+ levels at rest and after IgM cross-linking. These data support the hypothesis that CD5 negatively regulates Ig receptor signaling in anergic B cells and functions to inhibit autoimmune B cell responses.

Key Words: CD5 • hen egg lysozyme • B cell • anergy • signal transduction

Abbreviations used in this paper: [Ca2+]i, intracellular calcium concentration; BCR, B cell receptor; HEL, hen egg lysozyme; MFI, mean fluorescence intensity; mHEL, membrane-bound self-antigen HEL; sHEL, soluble self-antigen HEL; SHP-1, Src homology 2 domain–containing protein tyrosine phosphatase 1; Tg, transgenic.

© 2000 The Rockefeller University Press


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