Figure 4.

Proposed Model for Multiple Waves of Definitive Hematopoiesis Contributing to B-1a B Cells

Multiple overlapping waves of definitive hematopoiesis emerge within embryonic vessels between E9 and E11.5, giving rise initially to multilineage progenitors producing erythroid, myeloid, and innate-immune lymphoid progeny independently of HSC (Böiers et al., 2013, Godin et al., 1993, Inlay et al., 2014, Kobayashi et al., 2014, Yoshimoto et al., 2011, Yoshimoto et al., 2012), followed by emergence of the earliest clonal pre-HSCs giving rise to “developmentally restricted” HSCs with innate-immune biased lymphoid potential (Beaudin et al., 2016), and late pre-HSC clones giving rise to a pool of extensively self-renewing fetal liver HSCs that initially have limited B-1a B cell potential, which is lost as they establish the life-long HSC pool of the adult bone marrow (Ghosn et al., 2012).