Deficiency in CD22, a B cell-specific inhibitory receptor, is sufficient to predispose to development of high affinity autoantibodies.
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.
O'Keefe
T L
TL
Medical Research Council Laboratory of Molecular Biology, Cambridge CB2 2QH, United Kingdom.
Williams
G T
GT
Batista
F D
FD
Neuberger
M S
MS
D000367:Age Factors; D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000378:metabolism; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology*; D000944:Antigens, Differentiation, B-Lymphocyte / Q000235:genetics / Q000276:immunology*; D001323:Autoantibodies / Q000737:chemistry / Q000276:immunology*; D015551:Autoimmunity / Q000276:immunology; D001402:B-Lymphocytes / Q000378:metabolism*; D015374:Biosensing Techniques; D015815:Cell Adhesion Molecules; D004247:DNA / Q000276:immunology; D018390:Gene Targeting; D007074:Immunoglobulin G / Q000097:blood; D007135:Immunoglobulin Variable Region / Q000235:genetics / Q000276:immunology; D007700:Kinetics; D037102:Lectins; D051379:Mice; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D009154:Mutation; D011485:Protein Binding; D011956:Receptors, Cell Surface / Q000235:genetics / Q000276:immunology*; D051918:Sialic Acid Binding Ig-like Lectin 2
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; D001323:Autoantibodies; C497868:Cd22 protein, mouse; D015815:Cell Adhesion Molecules; D007074:Immunoglobulin G; D007135:Immunoglobulin Variable Region; D037102:Lectins; D011956:Receptors, Cell Surface; D051918:Sialic Acid Binding Ig-like Lectin 2; D004247:DNA