CHARACTERIZATION OF A HUMAN MONOCLONAL AUTOANTIBODY DIRECTED TO CARDIOLIPIN BETA(2)-GLYCOPROTEIN-I PRODUCED BY CHRONIC LYMPHOCYTIC-LEUKEMIAB-CELLS

We determined the specificity and sequence of immunoglobulin molecules synthesized by monoclonal B cells from a patient with chronic lymphoc ytic leukaemia (CLL) who presented with a number of clinical and biolo gical autoimmune symptoms. Heterohybrids obtained by fusion of CLL cel ls with the mouse X63-Ag 8.653 myeloma produced IgMlambda MoAbs direct ed to the cardiolipin/beta2 glycoprotein I (BETA2GPI) complex and ssDN A. They were devoid of polyreactivity. NucLeotide sequence analysis of the variable domain of the mu chain indicated the utilization of the V(H)4 71.2 gene or one allotypic variant, D(XP)p4 and J(H)3 segments. The lambda light chain used the single gene from the V(lambda)8 subfam ily, J(lambda)3 and C(lambda)3 genes. The V(H) gene displayed 11 nucle otide changes in comparison with its putative germline counterpart. Ho wever, these nucleotide changes correspond to variations observed in o ther published V(H)4 sequences, suggesting gene polymorphism rather th an somatic mutation. D(XP)4 and J(H)3 were also in germline configurat ion. The V(L) gene exhibited a single replacement mutation in CDR1. Th ese data suggest that the monoclonal CLL B cells in this patient retai ned V(H) and V(L) genes in germline configuration although they secret ed a pathogenic anti-cardiolipin antibody associated with clinical sym ptoms, vasculitis and thrombosis, which may be provoked by antibodies to the phospholipid/beta2GPI complex.