Asymmetric T Lymphocyte Division in the Initiation of Adaptive Immune Responses

TLDR

A hallmark of mammalian immunity is the heterogeneity of cell fate that exists among pathogen‑experienced lymphocytes. Asymmetric segregation of determinants appears to be coordinated by prolonged interaction between the T cell and its antigen‑presenting cell before division. We show that a dividing T lymphocyte initially responding to a microbe exhibits unequal partitioning of signaling, fate‑specifying, and asymmetric division proteins, and that its first two daughters display phenotypic and functional markers of divergent effector and memory fates, indicating a mechanism by which a single lymphocyte can apportion diverse cell fates necessary for adaptive immunity.

Abstract

A hallmark of mammalian immunity is the heterogeneity of cell fate that exists among pathogen-experienced lymphocytes. We show that a dividing T lymphocyte initially responding to a microbe exhibits unequal partitioning of proteins that mediate signaling, cell fate specification, and asymmetric cell division. Asymmetric segregation of determinants appears to be coordinated by prolonged interaction between the T cell and its antigen-presenting cell before division. Additionally, the first two daughter T cells displayed phenotypic and functional indicators of being differentially fated toward effector and memory lineages. These results suggest a mechanism by which a single lymphocyte can apportion diverse cell fates necessary for adaptive immunity.