A human anti-cardiolipin autoantibody is encoded by developementally restricted heavy and light chain variable region genes.
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.
Siminovitch
K A
KA
Department of Medicine, University of Toronto, Ontario, Canada.
Misener
V
V
Kwong
P C
PC
Yang
P M
PM
Laskin
C A
CA
Cairns
E
E
Bell
D
D
Rubin
L A
LA
Chen
P P
PP
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
D000911:Antibodies, Monoclonal; D001323:Autoantibodies; D002308:Cardiolipins; D007143:Immunoglobulin Heavy Chains; D007147:Immunoglobulin Light Chains; D007135:Immunoglobulin Variable Region