Two mechanisms of transferrin receptor induction by anti-Ig in B cells.

By cross-linking surface Ig to the Fc gamma R, whole (IgG)-rabbit anti-Ig antibodies have been shown to substantially inhibit proliferation induced by LPS and F(ab')2 anti-Ig, and polyphosphoinositide hydrolysis induced by F(ab')2 anti-Ig. Surprisingly, however, whole anti-Ig was unable to inhibit induction of transferrin receptor (TfR) expression by LPS or F(ab')2 anti-Ig. Indeed, whole anti-Ig on its own induced TfR as early as 4 h. TfR induction by F(ab')2 anti-Ig and by LPS was accompanied by an early increase in TfR mRNA, and was prevented by inhibitors of protein and RNA synthesis and therefore can be ascribed to a transcriptional mechanism. In contrast, whole anti-Ig induced TfR even in the presence of protein and RNA synthesis inhibitors. Little or no TfR mRNA was detectable after 4 or 16 h of exposure to whole anti-Ig, whereas increased TfR mRNA was evident after 4 h of F(ab')2 anti-Ig or LPS. Antibody to the Fc gamma R (2.4G2) restores the ability of whole anti-Ig to generate increased TfR expression via the transcriptional route. We conclude that whole anti-Ig induces TfR mostly by using preexisting TfR molecules through a mechanism different from the transcriptional mechanism triggered by F(ab')2 anti-Ig and LPS.