Immune Cell Identity: Perspective from a Palimpsest

The immune system in mammals is composed of multiple different immune cell types that migrate through the body and are made continuously throughout life. Lymphocytes and myeloid cells interact with each other and depend upon each other, but each are highly diverse and specialized for different roles. Lymphocytes uniquely require developmentally programmed mutational changes in the genome itself for their maturation. Despite profound differences between their mechanisms of threat recognition and threat response, however, the developmental origins of lymphocytes and myeloid cells are interlinked, and important aspects of their response mechanisms remain shared. It is notable that the chain of logic toward our current understanding of the immune defense system over the past 50 years has been driven by strongly posited models that have led to crucial discoveries, even though these models ended up being partly wrong. The predictive strength of these models and their success as guides to incisive experimental research have illuminated the limits of each model’s explanatory scope, beyond which another model needed to assume the lead. This brief review describes how a succession of distinct paradigms has helped to clarify a sophisticated picture of immune cell generation and control