Human monoclonal antibodies produced in transgenic BABκ,λ mice recognising idiotypic immunoglobulins of human lymphoma cells

Abstract

Clonal idiotypic immunoglobulins of follicular lymphomas can be isolated by somatic fusion procedures. Idiotypic IgMs (Id-IgM) were isolated from two patients and used to immunise a strain of mice, deficient in mouse antibody production and engineered with yeast artificial chromosomes (YAC) containing fragments of the human immunoglobulin (Ig) μ/δ heavy chain and κ/λ light chain loci. Sequence analysis showed that hybridomas prepared from spleen cells of immunised mice expressed exclusively one of the six VH genes (VH1-2) present in the YAC transgene with different D/J rearrangements, and secrete fully human monoclonal antibodies (mAb) that recognised the tumour-specific IgM proteins. Further studies of the reactivity of the monoclonal anti-human Id-IgM antibodies revealed that they are specific for the individual protein of each patient and probably react with idiotypic determinants. In one case studied, the antibody recognised specifically the lymphoma cell expressing the corresponding idiotypic IgM and lysed those cells in the presence of complement. This is the first example of a human monoclonal antibody with such characteristics and may be of further use in the therapy of patients with B cell malignancies. © 2004 Elsevier Ltd. All rights reserved.