Hirohata S
2nd Department of Internal Medicine, Teikyo University School of Medicine, Tokyo, Japan.
Cell Immunol. 1993 Aug;150(1):159-67. doi: 10.1006/cimm.1993.1187.
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.
用针对CD3分子复合物(64.1)的固定化单克隆抗体刺激的人CD4 + T细胞已被证明可通过抑制B细胞细胞周期的G1-S期转换对B细胞分化发挥抑制作用。本研究调查了抗CD3诱导的CD4 +抑制性T细胞对B细胞中DNA聚合酶α表达的影响。与用丝裂霉素C处理以消除抑制作用的固定化抗CD3刺激的CD4 + T细胞共培养的B细胞相比,在培养72小时后,与未用丝裂霉素C处理的固定化抗CD3刺激的CD4 + T细胞(对照T4细胞)共培养的B细胞中DNA聚合酶α的表达显著降低。从培养物中去除抗CD3激活的对照T4细胞后,B细胞中DNA聚合酶α表达的抑制是可逆的。增殖细胞核抗原的B细胞表达与DNA聚合酶δ的辅助蛋白密切相关,在培养的任何时间都不受抗CD3激活的对照T4细胞的抑制。因此,结果表明抗CD3诱导的CD4 +抑制性T细胞对人B细胞成熟的抑制与B细胞中DNA聚合酶α表达的抑制密切相关。此外,数据表明B细胞中DNA聚合酶α的活性和DNA聚合酶δ的活性可能是独立调节的。