A human monoclonal antiphospholipid antibody that is representative of serum antibodies and is germline encoded

Objective. To investigate the origins of antiphospholipid antibodies associated with thrombosis and other disorders that are found in patients with systemic lupus erythematosus and primary antiphospholipid syndrome (APS). Methods. Characterization, idiotypic study, and nucleotide sequencing of a human monoclonal antiphospholipid antibody generated from a patient with primary APS. Identification of the germline genes from which the antibody is derived. Results. A human monoclonal antibody, BH1, was generated. This antibody has ligand-binding properties that closely resemble those of the serum antiphospholipid antibodies found in our patient and in other individuals with APS: it recognizes negatively charged phospholipids, and has lupus anticoagulant activity; it does not bind to neutral phospholipids, or to singlestranded or double-stranded DNA. The relevance of BH1 to the patient's serum antibodies is supported by our idiotypic studies. BH1 is encoded by a new germline VH gene, and by a λ light chain gene that displays >99% homology with the VλIII.1 germline gene. Conclusion. Serum antiphospholipid antibodies associated with thrombosis may be encoded by either germline or only slightly mutated variable-region genes