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Dan Holmberg


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The Concerted Action of E2-2 and HEB Is Critical for Early Lymphoid Specification


  • Thibault Bouderlique
  • Lucia Peña-Pérez
  • Shabnam Kharazi
  • Miriam Hils
  • Xiaoze Li
  • Aleksandra Krstic
  • Ayla De Paepe
  • Christian Schachtrup
  • Charlotte Gustafsson
  • Dan Holmberg
  • Kristina Schachtrup
  • Robert Månsson

Summary, in English

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.


  • Autoimmunity
  • EXODIAB: Excellence of Diabetes Research in Sweden

Publishing year





Frontiers in Immunology



Document type

Journal article


Frontiers Media S. A.


  • Immunology
  • Cell and Molecular Biology


  • E-protein
  • evolution
  • hematopoiesis
  • humoral immunity
  • lymphoid specification



Research group

  • Autoimmunity


  • ISSN: 1664-3224