Ponnappan U, Cinader B, Gerber V, Blaser K
Department of Immunology, University of Toronto, Ontario, Canada.
Immunol Invest. 1992 Dec;21(7):637-48. doi: 10.3109/08820139209069400.
Aging is accompanied by changes in the immune system that occur at different levels and at different periods of time. We have studied age-related changes in isotype and idiotype of the antibody response to hapten phosphorylcholine (PC) in C57BL/6, and A mice and in the congenic MRL/Mp(-)+/+ and MRL/Mp-1pr/1pr strains. Three groups, representing young, middle and old age were immunized with PC-keyhole limpet hemocyanin. Total anti-PC antibody and the contribution of each isotype and of the T15 idiotype were assessed in the initial and late response. Some features of the antibody-response were similar in all the strains tested, e.g. the largest quantity of anti-PC antibody is formed in middle age and IgM is dominant in the initial response. However, remarkable differences occur in the isotype and idiotype predominance. Particularly, congenic MRL/Mp strains, prone to autoimmune disease, express the T15 idiotype only at low levels, even though IgM, which normally expresses this idiotype, is produced in large amounts. Furthermore, the late (memory) response of the MRL/Mp strains is dominated by IgG2b rather than IgG1, which is the predominant isotype in mice of long-lived strains. We conclude from these results that the number of T helper cells, involved in isotype regulation decreases with age and that there is a genetic variation, i.e., polymorphism in the ability to express T15-idiotype producing subtypes.
衰老伴随着免疫系统在不同水平和不同时期发生的变化。我们研究了C57BL/6、A小鼠以及同基因MRL/Mp(-)+/+和MRL/Mp-1pr/1pr品系中对半抗原磷酸胆碱(PC)抗体反应的同种型和独特型的年龄相关变化。将代表青年、中年和老年的三组小鼠用PC-钥孔戚血蓝蛋白免疫。在初始反应和后期反应中评估总抗PC抗体以及每种同种型和T15独特型的贡献。在所有测试品系中,抗体反应的一些特征是相似的,例如,中年时形成的抗PC抗体数量最多,并且在初始反应中IgM占主导地位。然而,在同种型和独特型优势方面存在显著差异。特别是,易患自身免疫性疾病的同基因MRL/Mp品系仅在低水平表达T15独特型,尽管通常表达这种独特型的IgM大量产生。此外,MRL/Mp品系的后期(记忆)反应以IgG2b而非IgG1为主导,而IgG1是长寿品系小鼠中的主要同种型。我们从这些结果得出结论,参与同种型调节的辅助性T细胞数量随年龄增长而减少,并且存在遗传变异,即在表达产生T15独特型亚型的能力方面存在多态性。