A Human Anti-Cardiolipin Autoantibody is Encoded by Developmentally restricted Heavy and Light Chain Variable Region Genes

Katherine a. Siminovitch Department of Medicine, University of Toronto, Toronto, Ontario, M5G 1X5, Canada; Department of Medicine, University of Western Ontario, London, Ontario, N6A 5A5

Virginia Misener Department of Medicine, University of Toronto, Toronto, Ontario, M5G 1X5, Canada; Department of Medicine, University of Western Ontario, London, Ontario, N6A 5A5

Pak C. Kwong Department of Medicine, University of Toronto, Toronto, Ontario, M5G 1X5, Canada; Department of Medicine, University of Western Ontario, London, Ontario, N6A 5A5

Pei-Ming Yang Department of Medicine, University of Toronto, Toronto, Ontario, M5G 1X5, Canada; Department of Medicine, University of Western Ontario, London, Ontario, N6A 5A5

Carl A. Laskin Department of Molecular and Experimental Medicine, Research Institute of Scripps Clinic, 10666 North Torrey Pines Road, La Jolla, California, 92037; Department of Medicine, University of Western Ontario, London, Ontario, N6A 5A5

Ewa Cairns Department of Molecular and Experimental Medicine, Research Institute of Scripps Clinic, 10666 North Torrey Pines Road, La Jolla, California, 92037; Department of Medicine, University of Western Ontario, London, Ontario, N6A 5A5

David Bell Department of Molecular and Experimental Medicine, Research Institute of Scripps Clinic, 10666 North Torrey Pines Road, La Jolla, California, 92037; Department of Medicine, University of Western Ontario, London, Ontario, N6A 5A5

Laurence A. Rubin Department of Medicine, University of Toronto, Toronto, Ontario, M5G 1X5, Canada; Department of Medicine, University of Western Ontario, London, Ontario, N6A 5A5

Pojen P. Chen Department of Medicine, University of Toronto, Toronto, Ontario, M5G 1X5, Canada; Department of Medicine, University of Western Ontario, London, Ontario, N6A 5A5

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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.

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A Human Anti-Cardiolipin Autoantibody is Encoded by Developmentally restricted Heavy and Light Chain Variable Region Genes

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A Human Anti-Cardiolipin Autoantibody is Encoded by Developmentally restricted Heavy and Light Chain Variable Region Genes

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