Proposed sources of tissue-resident B1a cells. The cellular origins of B1a cells have been debated since they were first identified as atypical B cells with unique functions and origins. (A) Early experiments led to the conclusion that fetal hematopoietic cells have superior B1a reconstitution capability compared with adult cells.^10,14  (B) In 2016, Ghosn et al reported that the majority of B1a repopulation potential is provided by fetal putative progenitor cells as opposed to strictly defined fetal liver HSCs.²²  (C) Montecino-Rodriguez et al, using a PU.1 hypomorph model, concluded that the first B1-cell generation is established prior to the existence of engraftable HSCs, with additional waves contributing during fetal and adult life.²⁹  (D) Kristiansen et al used bar coding and single-cell transplantation³¹  to demonstrate that fetal HSCs are clonally capable of B1a-cell generation upon transplantation into adult recipients, whereas adult HSCs contributed little to B1a repopulation. (E) Beaudin et al showed that a small pool of drHSCs are uniquely apt to generate B1a cells compared with coexisting fetal liver HSCs, or adult BM HSCs.³²  (F) Sawai et al used an HSC-specific pulse-labeling strategy to show that adult HSCs contribute minimally to B1a cells under homeostatic or interferon-challenged conditions in situ.³⁵  HSPC, hematopoietic stem and progenitor cell; MPP, multipotent progenitor cell. An “f” prefix indicates fetal, an “a” indicates adult, and “dr” indicates developmentally restricted.