To B1a or not to B1a: do hematopoietic stem cells contribute to tissue-resident immune cells?

Hematopoietic stem cells (HSCs) have long been considered the continuous source of all hematopoietic cells for the life of an individual. Recent findings have questioned multiple aspects of this view, including the ability of lifelong HSCs to contribute to tissue-resident immune cells. Here we discuss the most recent findings on the source of B1a cells, innatelike lymphocytes that primarily reside in serous cavities. Powerful experimental approaches including bar coding, single cell transplantation, in vivo lineage tracing, and HSC-specific pulse-chase labeling have provided novel insights on B1a-cell generation during ontogeny. We evaluate the evidence for fetal vs adult B1a-cell production capacity and the identity of putative cells of origin. Integrating these most recent findings with previous work, we propose a working model that encapsulates our current understanding of waves of immune development.