MODULATION OF TRANSFERRIN RECEPTOR EXPRESSION AND FUNCTION BY ANTI-TRANSFERRIN RECEPTOR ANTIBODIES AND ANTIBODY FRAGMENTS
MODULATION OF TRANSFERRIN RECEPTOR EXPRESSION AND FUNCTION BY ANTI-TRANSFERRIN RECEPTOR ANTIBODIES AND ANTIBODY FRAGMENTS
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DOI：
10.1016/0014-4827(89)90293-0
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发表时间：
1989-05-01
影响因子：
3.7
通讯作者：
WOODS, J
中科院分区：
文献类型：
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作者：
LESLEY, J;SCHULTE, R;WOODS, J
已经表明，抗转铁蛋白受体抗体对细胞生长和受体表达的影响是由二价和多价结合剂引起的不同程度的受体交联的结果。为了直接研究这个问题，我们培养了鼠淋巴瘤细胞的IgG和IgM单克隆抗转铁蛋白受体抗体和完整的抗体的单和二价片段。本文提出的研究表明，抗体结合对转移受体分布、代谢和功能的影响至少部分取决于抗体效价，因此取决于抗体与受体的交联程度。我们发现，单价抗体片段没有显着改变细胞生长，受体表面表达，细胞内定位，或降解。二价抗体引起的细胞表面受体表达的均匀下调，这是伴随着增加的降解，只有当抗体Fc存在。尽管表面表达减少，但正常的受体循环明显继续。然而，在多价IgM抗体中培养导致抗体复合受体在细胞表面上积累而不内化，并引起细胞生长的深刻抑制。因此，我们显示了两种不同程度的抗体交联可以影响转铁蛋白受体功能的机制：受体下调和阻断内化。
It has been suggested that effects of anti-transferrin receptor antibodies on cell growth and receptor expression are the result of varying degrees of receptor crosslinking by bi- and multivalent binding agents. In order to study this question directly, we have cultured murine lymphoma cells in mono- and divalent fragments from IgG and IgM monoclonal anti-transferrin receptor antibodies and in intact antibodies. The studies presented here demonstrate that effects of antibody binding on transferring receptor distribution, metabolism, and function depend, at least in part, on antibody valence, and therefore on the degree of crosslinking or receptors by antibody. We found that monovalent antibody fragments did not significantly alter cell growth, receptor surface expression, intracellular localization, or degradation. Divalent antibody caused a uniform down-regulation of cell-surface receptor expression, which was accompanied by increased degradation only when antibody Fc was present. Normal receptor cycling apparently continued, despite the reduction in surface expression. Culture in multivalent IgM antibody, however, resulted in accumulation of antibody-complexed receptor on the cell surface without internalization and caused profound inhibition of cell growth. Thus, we show two mechanisms by which different degrees of antibody crosslinking can influence transferrin receptor function: by receptor down-regulation and blocking internalization.