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© The Rockefeller University Press, 0022-1007/1999/4/1307/ $5.00
The Journal of Experimental Medicine, Volume 189, Number 8, April 19, 1999 1307-1313

Articles

Deficiency in CD22, a B Cell–specific Inhibitory Receptor, Is Sufficient to Predispose to Development of High Affinity Autoantibodies

Theresa L. O'Keefe, Gareth T. Williams, Facundo D. Batista, and Michael S. Neuberger

From the Medical Research Council Laboratory of Molecular Biology, Cambridge CB2 2QH, United Kingdom

CD22 is a B cell–specific transmembrane glycoprotein that acts to dampen signals generated through the B cell antigen receptor (BCR): B cells from CD22-deficient mice give increased Ca2+ fluxes on BCR ligation. Here we show that this B cell hyperresponsiveness correlates with the development of autoantibodies. After the age of eight months, CD22-deficient mice developed high titers of serum IgG directed against double-stranded DNA; these antibodies were of multiclonal origin, somatically mutated, and high affinity. Increased titers of antibodies to cardiolipin and myeloperoxidase were also noted. The results demonstrate that a single gene defect exclusive to B lymphocytes is, without additional contrivance, sufficient to trigger autoantibody development in a large proportion of aging animals. Thus, CD22 might have evolved specifically to regulate B cell triggering thresholds for the avoidance of autoimmunity.

Key Words: B lymphocyte • autoimmunity • threshold • CD22 • inhibitory receptor

Address correspondence to Michael Neuberger, MRC Laboratory of Molecular Biology, Hills Road, Cambridge CB2 2QH, United Kingdom. Phone: 44-1223-402245; Fax: 44-1223-412178; E-mail: msn{at}mrc-lmb.cam.ac.uk

T.L. O'Keefe was supported by an Oliver Bird Fund fellowship and an International Research Scholar's award from the Howard Hughes Medical Institute (to M.S. Neuberger). F.D. Batista was supported by fellowships from the European Molecular Biology Organization and the Arthritis Research Campaign.

Theresa L. O'Keefe's present address is LeukoSite Inc., 215 First Street, Cambridge, MA 02144.

Abbreviations used: BCR, B cell antigen receptor; ds, double-stranded; ES, embryonic stem cell.


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