Mizuguchi J, Beaven M A, Li J H, Paul W E
Proc Natl Acad Sci U S A. 1986 Jun;83(12):4474-8. doi: 10.1073/pnas.83.12.4474.
Cross-linking the membrane immunoglobulins of resting B cells leads to activation as judged by increased inositol phospholipid metabolism, intracellular free calcium concentration ([Ca2+]i), and cell volume. Such activated B cells enter S phase in the presence of B-cell stimulatory factor 1. Phorbol myristate acetate (PMA) is a potent inhibitor of anti-IgM- and anti-IgD-stimulated B-cell responses. In B cells concentrations of PMA ranging from 0.1 to 100 ng/ml completely inhibit anti-IgM-stimulated DNA synthesis and block anti-IgM-stimulated increases in inositol phospholipid metabolism and in [Ca2+]i. Preincubation periods as short as 4 min block these effects although longer preincubations are somewhat more effective in inhibiting increases in [Ca2+]i. Preincubation with PMA for 1.5 hr does not diminish expression of membrane IgM. This strongly suggests that PMA inhibits responses of resting B cells to anti-IgM by interrupting signal transmission rather than by diminishing cross-linking of membrane immunoglobulin on B cells. In contrast to resting B cells, B cells activated in vitro for 29 hr show enhanced responses to anti-IgM in the presence of PMA.
通过增加肌醇磷脂代谢、细胞内游离钙浓度（[Ca2+]i）和细胞体积来判断，使静止B细胞的膜免疫球蛋白发生交联会导致细胞活化。这种活化的B细胞在存在B细胞刺激因子1的情况下进入S期。佛波酯（PMA）是抗IgM和抗IgD刺激的B细胞反应的有效抑制剂。在B细胞中，浓度范围为0.1至100 ng/ml的PMA完全抑制抗IgM刺激的DNA合成，并阻断抗IgM刺激的肌醇磷脂代谢和[Ca2+]i的增加。预孵育时间短至4分钟即可阻断这些效应，尽管较长时间的预孵育在抑制[Ca2+]i增加方面更有效。用PMA预孵育1.5小时不会减少膜IgM的表达。这强烈表明，PMA通过中断信号传递而非减少B细胞膜上免疫球蛋白的交联来抑制静止B细胞对抗IgM的反应。与静止B细胞相反，体外活化29小时的B细胞在存在PMA的情况下对抗IgM的反应增强。
