Open AccessCharacterization of a human monoclonal autoantibody directed to cardiolipin/β 2 glycoprotein I produced by chronic lymphocytic leukaemia B cells
Author(s) -
MARIETTE X.,
LEVY Y.,
DUBREUIL M.L.,
INTRATOR L.,
DA F.,
BROUET J.C.
Publication year - 1993
Publication title -
clinical & experimental immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.329
H-Index - 135
eISSN - 1365-2249
pISSN - 0009-9104
DOI - 10.1111/j.1365-2249.1993.tb03461.x
Subject(s) - biology , microbiology and biotechnology , germline , cardiolipin , germline mutation , immunoglobulin light chain , monoclonal antibody , epitope , monoclonal , gene , antibody , mutation , immunology , genetics , phospholipid , membrane
SUMMARY We determined the specificity and sequence of immunoglobulin molecules synthesized by monoclonal B cells from a patient with chronic lymphocytic leukaemia (CLL) who presented with a number of clinical and biological autoimmune symptoms. Helerohybrids obtained by fusion of CLL cells with the mouse X63‐Ag 8.653 myeloma produced IgMλ MoAbs directed to the cardiolipin/β 2 glycoprotein I (β2GPI) complex and ssDNA. They were devoid of polyreactivity. Nuclcotide sequence analysis of the variable domain of the μ chain indicated the utilization of the V H 4 71.2 gene or one allotypic variant, D Xp 4 and J H 3 segments. The λ light chain used the single gene from the V λ8 subfamily, J λ 3 and C λ 3 genes. The V H gene displayed 11 nucleotide changes in comparison with its putative germline counterpart. However, these nucleotide changes correspond to variations observed in other published V H 4 sequences, suggesting gene polymorphism ralher than somatic mutation. D xp 4 and J h 3 were also in germline configuration. The Vl gene exhibited a single replacement mutation in CDRl. These data suggest that the monoclonal CLLB cells in this patient retained V H and V L genes in germline configuration although they secreted a pathogenic anti‐cardiolipin antibody associated with clinical symptoms, vasculitis and thrombosis, which may be provoked by antibodies to the phospholipid/β2GPI complex.