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 immune system, we have studied the anti-dextran (Dx) B512 humoral immune response 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 impairment of TD responses. We conclude that the first antigenic challenge deeply influences further antigenic responses in a positive or negative manner. Priming 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 TD priming (CSA-Dx) provoked a long-lasting immune memory that abolished in part the age-associated impairment of the response. Our results suggest that protocols of vaccination with TI antigens may not be a convenient strategy, because the development of further optimal immune responses to the same antigen can be impaired.