Inhibition of B cell expression of DNA polymerase alpha by CD4+ suppressor T cells.
Human CD4+ T cells stimulated with immobilized monoclonal antibodies to the CD3 molecular complex (64.1) have been shown to exert suppressive effects on B cell differentiation by inhibiting the G1-S transition of the cell cycle of B cells. The present study investigates the influences of the anti-CD3-induced CD4+ suppressor T cells on the expression of DNA polymerase alpha in B cells. The expression of DNA polymerase alpha in B cells cocultured with immobilized anti-CD3-stimulated CD4+ T cells without mitomycin C treatment (control T4 cells) was significantly decreased after 72 hr of the cultures compared with that in B cells cocultured with immobilized anti-CD3-stimulated CD4+ T cells that had been treated with mitomycin C to abrogate the suppressive effects. The inhibition of the expression of DNA polymerase alpha in B cells was reversible upon removal of anti-CD3-activated control T4 cells from the culture. The B cell expression of proliferating cell nuclear antigen, which is closely related to the auxiliary protein for DNA polymerase delta, was not inhibited by anti-CD3-activated control T4 cells at any time of the cultures. Thus, the results demonstrate that the suppression of human B cell maturation by the anti-CD3-induced CD4+ suppressor T cells is closely related with the inhibition of the expression of DNA polymerase alpha in B cells. Moreover, the data suggest that the activity of DNA polymerase alpha and that of DNA polymerase delta in B cells might be independently regulated.
Hirohata
S
S
2nd Department of Internal Medicine, Teikyo University School of Medicine, Tokyo, Japan.
D000328:Adult; D001402:B-Lymphocytes / Q000201:enzymology*; D017252:CD3 Complex / Q000502:physiology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D004257:DNA Polymerase II / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D008213:Lymphocyte Activation; D009687:Nuclear Proteins / Q000378:metabolism; D018809:Proliferating Cell Nuclear Antigen; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
D017252:CD3 Complex; D009687:Nuclear Proteins; D018809:Proliferating Cell Nuclear Antigen; D004257:DNA Polymerase II