Asymmetric division and stem cell renewal without a permanent niche: lessons from lymphocytes

Numerous tissues in long-lived organisms are composed of short-lived cells. The continual regeneration of some barrier surfaces, for example, relies on adult stem cells that have the capacity to divide and produce one daughter cell destined for terminal differentiation and function and another daughter cell that renews the stem cell fate. The immune system of higher animals possesses a cellular component called lymphocytes, which face a similar need for regeneration. A lymphocyte that is recruited during an infection must give rise to cellular progeny that undergo terminal differentiation to eliminate an invading microbe, yet retain progeny that replace the recruited cell in order to maintain immunity to reinfection. Emerging evidence suggests that specifying the divergent cell fates necessary for immunity relies on the ability of the lymphocyte to exploit an evolutionarily conserved strategy for making kindred cells different--asymmetric cell division. Although the lymphocyte does not possess constitutive polarity, it appears to use a facultative interaction with another cell to nucleate unequal segregation of fate determinants relative to its plane of division. Herein, we propose that other mobile and nonadherent cells, such as blood and cancer stem cells, might exploit provisional interactions with their niche or microenvironment to achieve diversity among their daughter cells.