Gebhardt B M, Nakao Y, Smith R T
J Exp Med. 1974 Aug 1;140(2):370-82. doi: 10.1084/jem.140.2.370.
Proliferation of F(1) hybrid lymphocytes in mixed lymphocyte cultures is stimulated by mitomycin-blocked parental cells. The demonstration of this phenomenon using F(1) hybrids derived from congenic lines of mice establishes that the stimulation is controlled by genes in or closely linked to the major histocompatibility locus chromosome region. In agreement with the finding that tumor-bearing mice have an increased capacity for primary alloantigen recognition, it was observed that the F(1) hybrid response to parent was also augmented by tumor bearing. Chromosomal analysis of dividing cells in one-way mixed cultures confirms that F(1) cells, and not the blocked parental cells, enter mitosis. Stimulation of F(1) cells by a soluble mediator liberated by the parental cells was not observed and mitomycin blocking of parental cells seems to be a completely effective blocking agent ensuring that parental cells can not enter DNA synthesis. The specificity and clonal nature of F(1) recognition of parent was demonstrated using a 5-bromodeoxyuridine-suicide procedure. Distinct clones of lymphocytes in F(1) spleen cell populations seem to recognize one or the other parent, but not both, in such experiments. These observations and others in tumor systems suggest that most or all heterozygous organisms may possess potentially self-reactive clones of lymphocytes.
在混合淋巴细胞培养中，丝裂霉素处理的亲代细胞可刺激F(1)杂种淋巴细胞增殖。利用源自近交系小鼠的F(1)杂种证明了这一现象，表明这种刺激受主要组织相容性位点染色体区域内或与之紧密连锁的基因控制。与荷瘤小鼠对初次同种异体抗原识别能力增强的发现一致，观察到荷瘤也增强了F(1)杂种对亲代的反应。单向混合培养中分裂细胞的染色体分析证实是F(1)细胞而非经处理的亲代细胞进入有丝分裂。未观察到亲代细胞释放的可溶性介质对F(1)细胞的刺激作用，亲代细胞的丝裂霉素处理似乎是一种完全有效的阻断剂，可确保亲代细胞不能进入DNA合成。使用5-溴脱氧尿苷自杀程序证明了F(1)对亲代识别的特异性和克隆性质。在这类实验中，F(1)脾细胞群体中不同的淋巴细胞克隆似乎只识别一方亲代，而非双方。肿瘤系统中的这些及其他观察结果表明，大多数或所有杂合生物体可能都拥有潜在的自身反应性淋巴细胞克隆。
