title: A human anti-cardiolipin autoantibody is encoded by developementally restricted heavy and light chain variable region genes.
abstract: Based on recent structural analyses of monoclonal autoantibodies, it appears that a number of these antibodies express germ-line immunoglobulin variable region (V) genes with little or no somatic mutation. In addition, our group and others have noted the identity or near identity of some autoantibody-associated V genes to V genes apparently expressed preferentially in the fetal pre-B cell repertoire. To extend these data, we now report that the heavy and light chain V genes of an anti-cardiolipin antibody derived from a healthy individual display 99% nucleotide sequence homology with V genes expressed in early B cell ontogeny. Sequence comparisons indicate the likely use of fetal-restricted V genes by this autoantibody. Taken together with other data on autoantibody V gene usage, these findings provide further evidence for overlap between the autoantibody-associated and early ontogeny expressed V gene repertoires and suggest that natural autoreactivity may be instrumental in the development and maintenance of the normal immune repertoire.
authors: Department of Medicine, University of Toronto, Ontario, Canada.
authors: K A
authors: KA
authors: Siminovitch
authors: V
authors: V
authors: Misener
authors: P C
authors: PC
authors: Kwong
authors: P M
authors: PM
authors: Yang
authors: C A
authors: CA
authors: Laskin
authors: E
authors: E
authors: Cairns
authors: D
authors: D
authors: Bell
authors: L A
authors: LA
authors: Rubin
authors: P P
authors: PP
authors: Chen
mesh_terms: D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000235:genetics; D001323:Autoantibodies / Q000235:genetics*; D001402:B-Lymphocytes / Q000276:immunology; D001483:Base Sequence; D002308:Cardiolipins / Q000276:immunology*; D003001:Cloning, Molecular; D015321:Gene Rearrangement / Q000276:immunology; D006801:Humans; D006825:Hybridomas; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D007147:Immunoglobulin Light Chains / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000235:genetics*; D008969:Molecular Sequence Data; D016415:Sequence Alignment; D012689:Sequence Homology, Nucleic Acid
chemical_list: D000911:Antibodies, Monoclonal; D001323:Autoantibodies; D002308:Cardiolipins; D007143:Immunoglobulin Heavy Chains; D007147:Immunoglobulin Light Chains; D007135:Immunoglobulin Variable Region