AUTHOR=Bouderlique Thibault , Peña-Pérez Lucia , Kharazi Shabnam , Hils Miriam , Li Xiaoze , Krstic Aleksandra , De Paepe Ayla , Schachtrup Christian , Gustafsson Charlotte , Holmberg Dan , Schachtrup Kristina , Månsson Robert TITLE=The Concerted Action of E2-2 and HEB Is Critical for Early Lymphoid Specification JOURNAL=Frontiers in Immunology VOLUME=10 YEAR=2019 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2019.00455 DOI=10.3389/fimmu.2019.00455 ISSN=1664-3224 ABSTRACT=

The apparition of adaptive immunity in Gnathostomata correlates with the expansion of the E-protein family to encompass E2-2, HEB, and E2A. Within the family, E2-2 and HEB are more closely evolutionarily related but their concerted action in hematopoiesis remains to be explored. Here we show that the combined disruption of E2-2 and HEB results in failure to express the early lymphoid program in Common lymphoid precursors (CLPs) and a near complete block in B-cell development. In the thymus, Early T-cell progenitors (ETPs) were reduced and T-cell development perturbed, resulting in reduced CD4 T- and increased γδ T-cell numbers. In contrast, hematopoietic stem cells (HSCs), erythro-myeloid progenitors, and innate immune cells were unaffected showing that E2-2 and HEB are dispensable for the ancestral hematopoietic lineages. Taken together, this E-protein dependence suggests that the appearance of the full Gnathostomata E-protein repertoire was critical to reinforce the gene regulatory circuits that drove the emergence and expansion of the lineages constituting humoral immunity.