Comparison of the effector functions of human immunoglobulins using a matched set of chimeric antibodies.

TLDR

The authors engineered mouse plasmacytoma cell lines to secrete matched human chimeric IgM, IgG1–4, IgE, and IgA2 antibodies against 4‑hydroxy‑3‑nitrophenacetyl and compared their C1q binding and complement‑mediated erythrocyte lysis. The chimeric IgG1 antibody exhibited superior complement‑dependent hemolysis and antibody‑dependent cell‑mediated cytotoxicity, outperforming other IgG subclasses despite IgG3’s higher C1q binding, indicating IgG1 as the preferred subclass for therapeutic use.

Abstract

Cell lines have been established that secrete a matched set of human chimeric IgM, IgG1, IgG2, IgG3, IgG4, IgE, and IgA2 antibodies that are directed against the hapten 4-hydroxy-3-nitrophenacetyl. These chimeric antibodies secreted from mouse plasmacytoma cells behave exactly like their authentic human counterparts in SDS-PAGE analysis, binding to protein A and in a wide range of serological assays. The antibodies have been compared in their ability to bind human C1q as well as in their efficacy in mediating lysis of human erythrocytes in the presence of human complement. A major conclusion to emerge is that whereas IgG3 bound C1q better than did IgG1, the chimeric IgG1 was much more effective than all the other IgG subclasses in complement-dependent hemolysis. The IgG1 antibody was also the most effective in mediating antibody-dependent cell-mediated cytotoxicity using both human effector and human target cells. These results suggest that IgG1 might be the favoured IgG subclass for therapeutic applications.