Ramirez R, Carracedo J, Mooney N, Charron D
Laboratory of Molecular Immunogenetics, Biomedical Institute of Cordeliers, Paris, France.
Hum Immunol. 1992 Jun;34(2):115-25. doi: 10.1016/0198-8859(92)90037-n.
Homotypic aggregation of B-lymphocytes, B-cell lines and class-II-positive T cells via HLA class II molecules was examined. Signaling via DR antigens induced rapid aggregation in a dose- and time-dependent manner, maximum and stable aggregation was induced within 20 minutes. On the contrary, rapid signaling via DP or DQ required prestimulation with either PMA or anti-sIg. Aggregation was temperature and energy dependent. [Ca2+] and [Mg2+] concentrations and an intact cytoskeleton were required while neither mRNA or protein synthesis were required. Furthermore, FACS analysis revealed that aggregation was not directly correlated with cell surface expression of HLA class II molecules. Our results demonstrate that aggregation was mediated through a protein tyrosine kinase (PTK)-dependent pathway that preceded activation of protein kinase C (PKC) and failure to generate either the PTK signal or the PKC signal prevented aggregation. The contribution of a tyrosine kinase was further demonstrated by the total inhibition of aggregation following treatment with an anti-CD45 mAb.
研究了通过HLA II类分子介导的B淋巴细胞、B细胞系和II类阳性T细胞的同型聚集。通过DR抗原的信号传导以剂量和时间依赖性方式诱导快速聚集，在20分钟内诱导最大且稳定的聚集。相反，通过DP或DQ的快速信号传导需要用PMA或抗sIg进行预刺激。聚集是温度和能量依赖性的。需要[Ca2+]和[Mg2+]浓度以及完整的细胞骨架，而不需要mRNA或蛋白质合成。此外，FACS分析显示聚集与HLA II类分子的细胞表面表达没有直接相关性。我们的结果表明，聚集是通过蛋白酪氨酸激酶（PTK）依赖性途径介导的，该途径先于蛋白激酶C（PKC）的激活，并且未能产生PTK信号或PKC信号会阻止聚集。用抗CD45 mAb处理后聚集的完全抑制进一步证明了酪氨酸激酶的作用。
