Elsevier

Journal of Autoimmunity

Volume 10, Issue 1, February 1997, Pages 43-57
Journal of Autoimmunity

Regular Article
The Production, Binding Characteristics and Sequence Analysis of Four Human IgG Monoclonal Antiphospholipid Antibodies

https://doi.org/10.1006/jaut.1996.0106Get rights and content

Abstract

Antiphospholid antibodies (APL) have a notable association with recurrent miscarriages, arterial and venous thrombosis and thrombocytopenia. Analysis of the potential pathogenic effects of such human antibodies has been hampered by the considerable difficulty in producing lgG as opposed to lgM monoclonal immunoglobulins. We have developed four human monoclonal lgG APL (LJ1, AH2, DA3 and UK4) by fusing the peripheral blood lymphocytes of three patients with SLE with a mouse human hetero-myeloma cell line, CB-F7. These antibodies bind to a variety of anionic phospholipids, two (LJ1 and AH2) bind total histones but none binds to ssDNA or dsDNA. Binding to β 2 GPI is non-specific. UK4 alone demonstrates lupus anticoagulant activity. All four have λ light chains, two are lgG1 (AH2 and UK4) and two are lgG3 (LJ1 and DA3). These APL utilize VHgenes present in the fetally restricted repertoire and multiple somatic mutations in the CDR suggest an antigen-driven process. In contrast, there is no restriction in Vλgene usage and only one lambda chain is extensively mutated. Two clonally related hybridomas were isolated from a single patient. This supports the theory that clonal expansion is the mechanism whereby antigen selects high affinity mutations.

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