Figure 3.

  The Imprinted Lifespan Model of long‐term antibody maintenance. As shown in Table 1 , antibody responses to specific virus and vaccine antigens have significantly different lifespans. Since plasma cells secrete antibody and consequently lose expression of the membrane‐bound forms of immunoglobulin, it is unlikely that they can detect or respond to specific antigen in their environment. It is thus suggested that the antigen‐specific imprinting of the antibody response must occur during the interface between B cells and antigen during the induction of the humoral immune response. In this model, the combined signals through the B‐cell receptor and signals obtained through CD4⁺ T‐cell help will dictate the lifespan of antibody‐secreting plasma cells. For instance, if B cells are exposed to soluble, non‐repetitive self protein or an unconjugated free chemical hapten, then there is no cross‐linking of the B‐cell receptor (BCR) and no T‐cell help, resulting in weak and short‐lived antibody responses. If the antigen is highly repetitive, then the BCR will be cross‐linked and increase signal strength to the responding B cell. However, without concomitant T‐cell help, the T‐cell‐independent antibody response remains short‐lived – in the order of a few weeks or months. In contrast, if the antigen contains foreign protein, then the responding B‐cell will receive critical CD4⁺ T‐cell help and induce an antibody response that could last for decades (e.g. tetanus toxoid). If the foreign protein antigen is also highly repetitive (e.g. a protein on the surface of a virus particle), then the combination of increased signaling through the BCR together with CD4⁺ T‐cell help will induce plasma cell progeny with an extended lifespan and potentially provide life‐long immunity against reinfection. Since many microbes have highly repetitive structures (identified through Toll‐like receptor as well as other pattern recognition receptors), the potential risk to the mammalian host is determined by the repetitive nature of the antigen and the availability of T‐cell help.