J. Exp. Med., Volume 189, Number 8, April 19, 1999 1307-1313

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

By 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.

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