Monoclonal antibodies from NZW x BXSB F1 mice to beta2 glycoprotein I and cardiolipin. Species specificity and charge-dependent binding.
NZW x BXSB F1 mice develop a systemic autoimmune syndrome with various lupus-like manifestations. Male animals develop a degenerative coronary disease with myocardial infarction, resulting in death before 6 mo of age. The presence in these mice of anti-phospholipid Abs reacting with beta2-glycoprotein I may contribute to the pathogenesis of the cardiovascular lesions. beta2-glycoprotein I, a plasma protein implicated in various aspects of the coagulation pathway, is also the target of autoantibodies in humans with the anti-phospholipid syndrome. We obtained several mAbs from NZW x BXSB F1 mice that were selected for binding to cardiolipin. Two mAbs are specific for beta2-glycoprotein I and display a species-dependent pattern with preferential reactivity to mouse beta2-glycoprotein I. The other mAbs display charge-mediated interactions with anionic phospholipids in the absence of beta2-glycoprotein I. The analysis of the V region sequences of the mAbs suggests that cationic residues in the H chain complementarity-determining region 3 are important for their phospholipid reactivity. The structural features of the V(H)-D-J(H) junctions of these mAbs further support the view that an increased frequency of unusual V(D)J rearrangements directly contributes to the development of murine autoimmunity.
Monestier
M
M
Department of Microbiology and Immunology, Temple University School of Medicine, Philadelphia, PA 19140, USA.
Kandiah
D A
DA
Kouts
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Novick
K E
KE
Ong
G L
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Radic
M Z
MZ
Krilis
S A
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D000595:Amino Acid Sequence; D000818:Animals; D017153:Antibodies, Anticardiolipin / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000918:Antibody Specificity; D001327:Autoimmune Diseases / Q000235:genetics / Q000276:immunology*; D001483:Base Sequence; D002308:Cardiolipins / Q000276:immunology*; D002417:Cattle; D004247:DNA / Q000235:genetics; D004563:Electrochemistry; D005260:Female; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain; D006023:Glycoproteins / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000235:genetics; D013045:Species Specificity; D013577:Syndrome; D053482:beta 2-Glycoprotein I
D017153:Antibodies, Anticardiolipin; D000911:Antibodies, Monoclonal; D002308:Cardiolipins; D006023:Glycoproteins; D007074:Immunoglobulin G; D012333:RNA, Messenger; D053482:beta 2-Glycoprotein I; D004247:DNA