Truman J P, Choqueux C, Charron D, Mooney N
INSERM U396, Immunogénétique Moléculaire, Institut Biomédical des Cordeliers, Paris, France.
Cell Immunol. 1996 Sep 15;172(2):149-57. doi: 10.1006/cimm.1996.0227.
The class II human leukocyte antigens (HLA class II) are constitutively expressed on antigen presenting cells (APC) and are essential for peptide presentation to helper T lymphocytes. Signal transduction by HLA class II molecules on B lymphocytes has been described and has been shown in many cases to induce cellular proliferation. However, since signalling via HLA class II can also lead to apoptosis, it has not been clear how the outcome of the signals is determined. We have distinguished two separate HLA class II-initiated pathways leading to either proliferation or apoptosis of primary human B lymphocytes. Proliferation requires new gene transcription and activation of src family tyrosine kinases. In contrast, apoptosis is significantly increased in the absence of transcription/translation. It is dependent on serine/threonine phosphatases and cytoskeletal mobility. An extracellular source of calcium was essential for apoptosis, suggesting the need for sustained high level of intracellular calcium. Activation of iso-enzymes of the protein kinase C family was needed for both pathways. We therefore conclude that HLA class II molecules can initiate two distinct signalling pathways leading to either proliferation or apoptosis of APC.
II类人类白细胞抗原（HLA - II类）在抗原呈递细胞（APC）上组成性表达，对于将肽呈递给辅助性T淋巴细胞至关重要。B淋巴细胞上HLA - II类分子的信号转导已被描述，并且在许多情况下已显示可诱导细胞增殖。然而，由于通过HLA - II类的信号传导也可导致细胞凋亡，因此尚不清楚信号的结果是如何确定的。我们已经区分出两条独立的由HLA - II类启动的途径，它们分别导致原代人B淋巴细胞的增殖或凋亡。增殖需要新的基因转录和src家族酪氨酸激酶的激活。相反，在没有转录/翻译的情况下，细胞凋亡显著增加。它依赖于丝氨酸/苏氨酸磷酸酶和细胞骨架的移动性。细胞外钙源对于细胞凋亡至关重要，这表明需要持续高水平的细胞内钙。蛋白激酶C家族的同工酶激活对于这两条途径都是必需的。因此，我们得出结论，HLA - II类分子可以启动两条不同的信号通路，分别导致APC的增殖或凋亡。
