Aging down‐regulates the transcription factor E2A, activation‐induced cytidine deaminase and Ig class switch in human B cells

Abstract

The capacity to class switch the Ig heavy chain is critical to the effectiveness of humoral immune responses in mice and humans. We have previously shown in mice that the E2A‐encoded transcription factor E47 is down‐regulated in old splenic B cells. This leads to a reduction in the activation‐induced cytidine deaminase (AID), which is known to induce class switch recombination (CSR) and Ig somatic hypermutation (SHM). We have extended our study here to investigate whether aging also affects antibody production, E47 and AID expression in B cells isolated from the peripheral blood (PB) of human subjects (18–86 years). Our results obtained with activated CD19+ B cells show that the expression of E47, AID and Igγ1 circle transcripts progressively decrease with age. We also show an age‐related decline in the percentage and numbers of switch memory B cells, no change in the percentage but a decline in the numbers of IgM memory B cells and an increase in the percentage but not in the numbers of naive B cells, consistent with our data on the decrease seen in CSR in vitro. In addition, we suggest that the subsets of B cells able to class switch in culture are the naïve and the IgM memory populatio, depending on the stimulus. Our results give possible molecular mechanisms for an intrinsic decrease in B cell function and the humoral immune response in aging.This work is supported by NIH AG‐17618, AG‐23717 (BBB) and AG025256 and AI064591 (RLR)