Mullins M W, Pittner B T, Snow E C
Department of Microbiology & Immunology, University of Kentucky Medical Center, Lexington 40536-0084, USA.
Mol Immunol. 1998 Jul;35(10):567-80. doi: 10.1016/s0161-5890(98)00038-8.
The accumulation of G1 cell cycle-related proteins by resting or cycling B cells stimulated with B cell antigen receptor (BCR)- and T helper (Th) cell-derived signals is documented. Resting B cells constitutively express cyclin dependent kinase (cdk)4, cdk2 and the cyclin dependent kinase inhibitor (CKI), p27. The initiation of optimal proliferation with F(ab')2 anti-mu plus paraformaldehyde-fixed CD40 ligand-baculovirus-infected Sf9 cells (CD40L/Sf9 cells) increases accumulation of both cdk4 and cdk2 while decreasing p27 levels. B cells express cyclin D2 early during cycle progression, while cyclin D3 and E are not expressed until 18 h poststimulation and cyclin A by 24 h poststimulation. Cycling B cells express heightened levels of all these cyclins and cdks. Although neither BCR- nor CD40-mediated signals appreciably alter cycling B cell accumulation of cyclins D2, cdk4 and cdk2, the absence of BCR-derived signals results in a decreased accumulation of cyclins D3 and E. Finally, CD40-mediated signals induce resting B cells to accumulate the CKI, p21, while cycling B cells require both BCR- and CD40-mediated signals to maintain increased expression of p21. Thus, a Th cell-derived signal may impact upon both resting and cycling B cell cycle progression, at least in part, by regulating the accumulation of p21. The functional consequences of p21 accumulation as cells enter and move through the cell cycle are discussed.
有文献记载，静息或处于细胞周期的B细胞在受到B细胞抗原受体（BCR）和辅助性T细胞（Th）来源的信号刺激后，会积累与G1细胞周期相关的蛋白质。静息B细胞组成性表达细胞周期蛋白依赖性激酶（cdk）4、cdk2以及细胞周期蛋白依赖性激酶抑制剂（CKI）p27。用F(ab')2抗μ加上经多聚甲醛固定的CD40配体-杆状病毒感染的Sf9细胞（CD40L/Sf9细胞）引发最佳增殖，会增加cdk4和cdk2的积累，同时降低p27水平。B细胞在细胞周期进程早期表达细胞周期蛋白D2，而细胞周期蛋白D3和E直到刺激后18小时才表达，细胞周期蛋白A在刺激后24小时才表达。处于细胞周期的B细胞表达所有这些细胞周期蛋白和cdk的水平更高。虽然BCR介导的信号和CD40介导的信号都不会明显改变处于细胞周期的B细胞中细胞周期蛋白D2、cdk4和cdk2的积累，但缺乏BCR来源的信号会导致细胞周期蛋白D3和E的积累减少。最后，CD40介导的信号诱导静息B细胞积累CKI p21，而处于细胞周期的B细胞需要BCR介导的信号和CD40介导的信号来维持p21的高表达。因此，Th细胞来源的信号可能至少部分地通过调节p21的积累来影响静息和处于细胞周期的B细胞的细胞周期进程。本文讨论了细胞进入并经历细胞周期时p21积累的功能后果。
