Reduced Ig class switch in aged mice correlates with decreased E47 and activation-induced cytidine deaminase.

The capacity to class switch the IgH chain is critical to the effectiveness of humoral immune responses. We show that in vitro-stimulated splenic B cells from senescent mice are deficient in production of multiple class switch isotypes (IgG1, G2a, G3, and E), class switch recombination (CSR), and induction of the E2A-encoded transcription factor E47. E47 has previously been shown to be required for CSR, at least in part via expression of the activation-induced cytidine deaminase. Our studies show that impaired induction of E47, and subsequently activation-induced cytidine deaminase, contribute to poor CSR and production of secondary isotypes in senescence.