Inheritance of immune responsiveness, life span, and disease incidence in interline crosses of mice selected for high or low multispecific antibody production.
Inheritance of immune responsiveness, life span, and disease incidence in interline crosses of mice selected for high or low multispecific antibody production.
复制标题
选择产生高或低多特异性抗体的小鼠间系杂交中免疫反应性、寿命和疾病发生率的遗传。
作者：
V. Covelli;D. Mouton;V. di Majo;Y. Bouthillier;C. Bangrazi;J. Mével;S. Rebessi;G. Doria;G. Biozzi
通过选择性育种分离的高（H）和低（L）抗体应答小鼠品系在对不同特异性Ag的抗体（Ab）应答方面存在最大品系间差异（一般遗传调节）。对H系、L系、F_1代、F_2代和回交分离群体的SRBC凝集素反应分析表明，抗体反应是由5 ~ 7个独立位点加性互作控制的多基因性状，高反应性状的不完全显性（44% ± 7%），环境因子的影响为30% ± 10%。H、L、F1、F2和回交群体的寿命与2-ME抗性凝集素反应呈正相关（r = 0.97，p <0.001），与2-ME敏感凝集素反应呈负相关（r = 0.95，p = 0.01）（群体间相关）。在不同群体的个体中也观察到类似的相关性，特别是在F1 × L回交中，其中最大的表型方差被发现。不同IgG同种型的ELISA滴定证实了Ab反应性和寿命之间的正相关（群体内相关性）。恶性淋巴瘤和慢性肾炎是两种最常见的疾病。这种疾病的年龄调整的发病率，这在很大程度上是受环境因素的影响，占较长的寿命的H，与L，小鼠种群。存活率在30%以下的个体的寿命主要由生理老化速率决定，是由3 ~ 7个独立基因座的累积互作控制的多基因性状，长寿性状完全显性，环境因素的影响约占60%。因此，我们有理由认为一般抗体反应性和寿命是由少数相同或紧密连锁的基因位点调节的多基因性状，而免疫反应性是对抗肿瘤和炎症性疾病的防御机制。
High (H) and low (L) antibody responder lines of mice separated by selective breeding present a maximal interline difference in antibody (Ab) response to Ag of different specificities (general genetic regulation). The analysis of SRBC agglutinin response in H line, L line, F1 hybrids, F2, and backcross segregants demonstrates that Ab responsiveness is a polygenic trait regulated by the additive interaction of 5 to 7 independent loci, with an incomplete dominance (44% +/- 7%) of the high response character, and a 30% +/- 10% impact of the environmental factors. The life span of H, L, F1, F2, and backcross populations is correlated positively with 2-ME-resistant agglutinin response (r = 0.97, p less than 0.001) and negatively with 2-ME-sensitive agglutinin response (r = 0.95, p = 0.01) (interpopulation correlation). Similar correlations are also observed in individuals of the various populations, especially in F1 x L backcross, in which the largest phenotypic variance is found. The positive correlation between Ab responsiveness and life span was confirmed by ELISA titration for distinct IgG isotypes (intrapopulation correlation). Malignant lymphomas and chronic nephritis were the two most common diseases observed. The age-adjusted incidence of such diseases, which is largely affected by environmental factors, accounts for the longer life span of H, as compared with L, mouse populations. The longevity of the 30% or less survivors, chiefly determined by the rate of physiologic aging, is a polygenic character regulated by the cumulative interaction of 3 to 7 independent loci, with a complete dominance of the long life trait and an impact of the environmental factors of about 60%. Thus we have grounds for regarding general Ab responsiveness and life span as polygenic traits regulated by a small number of identical or closely linked gene loci, and immune responsiveness as a defense mechanism against neoplastic and inflammatory diseases.