| Autor: |
Bouderlique T; Department of Laboratory Medicine, Center for Hematology and Regenerative Medicine, Karolinska Institutet, Stockholm, Sweden., Peña-Pérez L; Department of Laboratory Medicine, Center for Hematology and Regenerative Medicine, Karolinska Institutet, Stockholm, Sweden., Kharazi S; Department of Laboratory Medicine, Center for Hematology and Regenerative Medicine, Karolinska Institutet, Stockholm, Sweden., Hils M; Faculty of Medicine & Faculty of Biology, Center for Chronic Immunodeficiency, Medical Center, University of Freiburg, Freiburg, Germany., Li X; Department of Laboratory Medicine, Center for Hematology and Regenerative Medicine, Karolinska Institutet, Stockholm, Sweden., Krstic A; Department of Laboratory Medicine, Center for Hematology and Regenerative Medicine, Karolinska Institutet, Stockholm, Sweden., De Paepe A; Department of Laboratory Medicine, Center for Hematology and Regenerative Medicine, Karolinska Institutet, Stockholm, Sweden., Schachtrup C; Faculty of Medicine, Institute of Anatomy and Cell Biology, University of Freiburg, Freiburg, Germany., Gustafsson C; Department of Laboratory Medicine, Center for Hematology and Regenerative Medicine, Karolinska Institutet, Stockholm, Sweden., Holmberg D; Lund University Diabetes Center, Lund University, Malmö, Sweden., Schachtrup K; Faculty of Medicine & Faculty of Biology, Center for Chronic Immunodeficiency, Medical Center, University of Freiburg, Freiburg, Germany., Månsson R; Department of Laboratory Medicine, Center for Hematology and Regenerative Medicine, Karolinska Institutet, Stockholm, Sweden.; Hematology Center, Karolinska University Hospital, Stockholm, Sweden. |
| Abstrakt: |
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. |
