Asymmetric T Cell Division and the Self-renewal of Specific Immunity

During clonal selection of a T cell in response to infection of a host with an invasive pathogen, the host must respond by producing at least two required and disparate cell populations - one that is responsible for controlling the current infection and another that is required to retain the T cell clone for protection against future insults. This diversity within the T cell response may be generated through the use of asymmetric cell division. How T cells may use asymmetric division and to what extent this molecular process plays a role in adaptive immunity is not well understood. Here we suggest that asymmetric division during the initial T cell response segregates proteins by a unique mechanism that involves unequal degradation of a fate-determinate secondary to polarized segregation of the protein degradation machinery. Furthermore, we provide data to extend the principle of asymmetric division to the memory cell response, suggesting that certain antigen-experienced lymphocytes can re-iteratively undergo this process to generate diversity when once again faced with a pathogenic challenge. Together, these results suggest highly conserved principles of stem-cell biology may be regulating the generation of diversity in the adaptive immune response both during primary and recurrent infection.