Inhibition of B Cell Expression of DNA Polymerase α 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 α in B cells. The expression of DNA polymerase α 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 α 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 δ, 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 α in B cells. Moreover, the data suggest that the activity of DNA polymerase α and that of DNA polymerase δ in B cells might be independently regulated.