MONOCLONAL-ANTIBODIES FROM NZW X BXSB F1-MICE TO BETA(2)-GLYCOPROTEIN-I AND CARDIOLIPIN - SPECIES-SPECIFICITY AND CHARGE-DEPENDENT BINDING

NZW x BXSB F-1 mice develop a systemic autoimmune syndrome with variou s lupus-like manifestations, Male animals develop a degenerative coron ary disease with myocardial infarction, resulting in death before 6 mo of age, The presence in these mice of anti-phospholipid Abs reacting with beta(2)-glycoprotein I may contribute to the pathogenesis of the cardiovascular lesions, beta(2)-glycoprotein I, a plasma protein impli cated in various aspects of the coagulation pathway, is also the targe t of autoantibodies in humans with the anti-phospholipid syndrome, We obtained several mAbs from NZW x BXSB F, mice that were selected for b inding to cardiolipin, Two mAbs are specific for beta(2)-glycoprotein I and display a species-dependent pattern with preferential reactivity to mouse beta(2)-glycoprotein I, The other mAbs display charge-mediat ed interactions with anionic phospholipids in the absence of beta(2)-g lycoprotein I, The analysis of the V region sequences of the mAbs sugg ests that cationic residues in the H chain complementarity-determining region 3 are important for their phospholipid reactivity, The structu ral 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.