Lipoldová M, Kosarová M, Zajícová A, Holán V, Hart A A, Krulová M, Demant P
Institute of Molecular Genetics, Academy of Sciences, Czech Republic, Prague.
Immunogenetics. 1995;41(5):301-11. doi: 10.1007/BF00172155.
T lymphocytes of the strain BALB/cHeA exhibit a low proliferative response to IL-2 and a high response to the anti-CD3 monoclonal antibodies, while the strain STS/A lymphocyte response to these stimuli is the opposite. We analyzed the genetic basis of this strain difference, using a novel genetic tool: the recombinant congenic strains (RCS). Twenty BALB/c-c-STS/Dem (CcS/Dem) RCS were used, each containing a different random set of approximately 12.5% of the genes from STS and the remainder from BALB/c. Consequently, the genes participating in the multigenic control of a phenotypic difference between BALB/c and STS become separated into different CcS strains where they can be studied individually. The strain distribution patterns of the proliferative responses to IL-2 and anti-CD3 in the CcS strains are different, showing that different genes are involved. The large differences between individual CcS strains in response to IL-2 or anti-CD3 indicate that both reactions are controlled by a limited number of genes with a relatively large effect. The high proliferative response to IL-2 is a dominant characteristic. It is not caused by a larger major cell subset size, nor by a higher level of IL-2R expression. The response to anti-CD3 is known to be controlled by polymorphism in Fc gamma receptor 2 (Fcgr2) and the CcS strains carrying the low responder Fcgr2 allele indeed responded weakly. However, as these strains do respond to immobilized anti-CD3, while the STS strain does not, and as some CcS strains with the BALB/c allele of Fcgr2 are also low responders, additional gene(s) of the STS strain strongly depress the anti-CD3 response. In a backcross between the high responder and the low responder strains CcS-9 and CcS-11, one of these unknown genes was mapped to the chromosome 10 near D10Mit14. The CcS mouse strains which carry the STS alleles of genes controlling the proliferative response to IL-2 and anti-CD3 allow the future mapping, cloning, and functional analysis of these genes and the study of their biological effects in vivo.
BALB/cHeA品系的T淋巴细胞对白细胞介素-2（IL-2）表现出低增殖反应，而对抗CD3单克隆抗体表现出高反应，而STS/A品系淋巴细胞对这些刺激的反应则相反。我们使用一种新型遗传工具：重组近交系（RCS），分析了这种品系差异的遗传基础。使用了20个BALB/c-c-STS/Dem（CcS/Dem）RCS，每个RCS包含约12.5%来自STS的随机基因集，其余来自BALB/c。因此，参与BALB/c和STS之间表型差异多基因控制的基因被分离到不同的CcS品系中，在那里可以对它们进行单独研究。CcS品系中对IL-2和抗CD3增殖反应的品系分布模式不同，表明涉及不同的基因。各个CcS品系对IL-2或抗CD3的反应存在很大差异，这表明这两种反应都由数量有限但效应相对较大的基因控制。对IL-2的高增殖反应是一个显性特征。它不是由更大的主要细胞亚群大小引起的，也不是由更高水平的IL-2受体（IL-2R）表达引起的。已知对抗CD3的反应受Fcγ受体2（Fcgr2）多态性控制，携带低反应性Fcgr2等位基因的CcS品系确实反应较弱。然而，由于这些品系确实对固定化抗CD3有反应，而STS品系没有，并且由于一些具有Fcgr2的BALB/c等位基因的CcS品系也是低反应者，STS品系的其他基因强烈抑制抗CD3反应。在高反应品系和低反应品系CcS-9和CcS-11之间的回交中，其中一个未知基因被定位到10号染色体上靠近D10Mit14的位置。携带控制对IL-2和抗CD3增殖反应基因的STS等位基因的CcS小鼠品系，使得未来能够对这些基因进行定位、克隆和功能分析，并研究它们在体内的生物学效应。
