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.
Vora
A
A
Department of Internal Medicine, University of Iowa College of Medicine, Iowa City.
Stunz
L L
LL
Kemp
J D
JD
Ashman
R F
RF
D000818:Animals; D000841:Anisomycin / Q000494:pharmacology; D000943:Antigens, Differentiation / Q000502:physiology; D001402:B-Lymphocytes / Q000502:physiology*; D015638:Cytochalasin D / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D007140:Immunoglobulin Fab Fragments / Q000276:immunology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008213:Lymphocyte Activation; D051379:Mice; D010716:Phosphatidylinositols / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D011947:Receptors, Antigen, B-Cell / Q000502:physiology*; D011961:Receptors, Fc / Q000502:physiology; D017452:Receptors, IgG; D011990:Receptors, Transferrin / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors
D000943:Antigens, Differentiation; D007140:Immunoglobulin Fab Fragments; D008070:Lipopolysaccharides; D010716:Phosphatidylinositols; D012333:RNA, Messenger; D011947:Receptors, Antigen, B-Cell; D011961:Receptors, Fc; D017452:Receptors, IgG; D011990:Receptors, Transferrin; D003609:Dactinomycin; D015638:Cytochalasin D; D000841:Anisomycin