Inhibition of cell growth by monoclonal anti-transferrin receptor antibodies.
Five anti-murine transferrin receptor monoclonal antibodies have been characterized with respect to immunoglobulin class, effects on binding of transferrin, and effects on AKR1 lymphoma cell growth in vitro. The immunoglobulin M (IgM) antibodies, but not the IgG antibodies, prevent cell growth. We suggest that the profound effects of the IgM antibodies on cell growth are probably due to extensive cross-linking of cell surface receptors. In support of this, we are able to mimic the growth-inhibiting effects of the IgM antibodies by adding antiimmunoglobulin to an IgG antibody. By flow microfluorimetry, we show that an IgG antibody by itself induces up to a 10-fold downward regulation in the cell surface transferrin receptor, which is accompanied by accelerated receptor degradation. A similar downward regulation is seen in mutant cells resistant to growth inhibition by an IgM antibody, when grown in the selecting antibody. Wild-type cells grown in the presence of IgM antibody do not show receptor downward regulation. Inhibitory effects of antibody plus antiimmuoglobulin on mutant cells are also consistent with extensive cross-linking causing inhibition of growth.
D000818:Animals; D000911:Antibodies, Monoclonal; D000936:Antigen-Antibody Complex; D002455:Cell Division; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D006801:Humans; D007074:Immunoglobulin G; D008223:Lymphoma; D051379:Mice; D008806:Mice, Inbred AKR; D011956:Receptors, Cell Surface / Q000502:physiology*; D011990:Receptors, Transferrin; D013953:Thymus Neoplasms; D014168:Transferrin / Q000502:physiology*
D000911:Antibodies, Monoclonal; D000936:Antigen-Antibody Complex; D007074:Immunoglobulin G; D011956:Receptors, Cell Surface; D011990:Receptors, Transferrin; D014168:Transferrin