Spector N L, Samson W, Ryan C, Gribben J, Urba W, Welch W J, Nadler L M
Division of Tumor Immunology, Dana-Farber Cancer Institute, Boston, MA 02115.
J Immunol. 1992 Mar 15;148(6):1668-73.
A large number of protein and molecular markers have been identified that delineate the early stages of human B cell activation and proliferation. In contrast, few if any molecules are transiently expressed precisely as activated B cells stop proliferating and undergo growth arrest. We demonstrate that the low molecular weight heat shock protein (hsp28) exhibits unique induction kinetics that specifically demarcates this interval. After mitogenic activation of unstimulated splenic B cells, hsp28 protein and phosphorylation transiently increase coinciding precisely with the peak of cellular proliferation and the onset of growth arrest. Although most neoplastic B cells constitutively express hsp28, three cell lines were identified that were hsp28-. No differences in phenotype or growth kinetics were detected between hsp28+ and hsp28- neoplastic B cells demonstrating that hsp28 expression is not essential for cell growth. However, when treated with phorbol ester or heat shock, these hsp28- cell lines synthesize hsp28 followed by the onset growth arrest. The consistency with which hsp28 induction transiently delineates the interval from peak proliferation to the onset of growth arrest suggests hsp28 itself is likely to be involved in regulating this process.
大量蛋白质和分子标志物已被鉴定出来,它们描绘了人类B细胞活化和增殖的早期阶段。相比之下,在活化B细胞停止增殖并进入生长停滞阶段时,很少有分子会短暂表达。我们证明,低分子量热休克蛋白(hsp28)呈现出独特的诱导动力学,精确地界定了这个间隔期。在未刺激的脾B细胞经有丝分裂原激活后,hsp28蛋白和磷酸化水平短暂升高,与细胞增殖高峰和生长停滞的开始恰好吻合。尽管大多数肿瘤性B细胞组成性表达hsp28,但鉴定出了三株hsp28阴性的细胞系。在hsp28阳性和阴性肿瘤性B细胞之间未检测到表型或生长动力学上的差异,表明hsp28表达对细胞生长并非必需。然而,当用佛波酯或热休克处理时,这些hsp28阴性细胞系会合成hsp28,随后进入生长停滞。hsp28诱导能短暂界定从增殖高峰到生长停滞开始的间隔期,这种一致性表明hsp28本身可能参与调控这一过程。