The response in old mice: positive and negative immune memory after priming in early age

To analyze the effect of age in both B and T cell compartments of the immun e system, we have studied the anti-dextran (Dx) B512 humoral immune respons e in aged C57BL/6 mice. We have used Dx in its native form, which induces a thymus-independent (TI) response, or conjugated to chicken serum albumin ( CSA), which induces a thymus-dependent (TD) response. We have also analyzed the adjuvant effect of cholera toxin (CT) in both types of responses. Our results show that the B cell compartment is not greatly affected by age as demonstrated in the TI responses and that CT is a powerful adjuvant despite the age of the animals. However, we found a severe age-associated impairme nt of TD responses. We conclude that the first antigenic challenge deeply i nfluences further antigenic responses in a positive or negative manner. Pri ming in early life with native Dx (TI) inhibited late TD responses in aged mice, even when the primary immunization had occurred a long time ago. This negative memory affects posterior TD responses both in the quantity and in the affinity of the response. However, immunization at an early age with T D priming (CSA-Dx) provoked a long-lasting immune memory that abolished in part the age-associated impairment of the response. Our results suggest tha t protocols of vaccination with TI antigens may not be a convenient strateg y, because the development of further optimal immune responses to the same antigen can be impaired.