Lymphocyte Development - INSERM U668  


  HEADDr SIMOES DE BIVAR CUMANO Ana / cumano@pasteur.fr
  MEMBERSDr BANDEIRA Antonio / BURLEN-DEFRANOUX Odile / DESANTI Guillaume
Dr GODIN Isabelle / Dr GOLUB Rachel / Dr KIEUSSEIAN Aurélie / LALANNE Ana Ines
Dr MORDELET Elodie / Dr PEFFAULT DE LA TOUR Régis / PEREIRA DE SOUSA Ana Patricia
Dr PEREIRA Pablo / POSSOT Cécilie / Dr VIEIRA Paulo / Dr ZUBER Julien


  Annual Report

Hematopoietic cell development occurs through a succession of events involving hematopoietic stem cell generation, self-renewal, lineage commitment and differentiation. The different members of the Unit for Lymphocyte Development study in an integrative manner different aspects of hematopoietic and lymphocyte development. Hematopoietic Stem Cell generation. We have identified the site where hematopoietic stem cell generation occurs, in embryogenesis. The analysis of the environmental signals that determine the commitment of mesoderm derivatives into hematopoietic cells is crucial for the understanding of stem cell self-renewal and lineage determination and the environmental/hematopoietic progenitor interaction is now one of the main focus of our research.

B-cell development. After migration to the hematopoietic organs, differentiation of hematopoietic stem cells occurs through the contact with the supporting stromal environment. Surface bound signaling molecules and cytokines determine lymphoid and myeloid lineage commitment and differentiation. We have shown that the fetal spleen environment has particular properties preventing hematopoietic stem cell renewal and favoring myeloid versus lymphoid commitment In collaboration with J.P. DiSanto and C. Vosshenrich we determined that B lymphocyte production have different cytokine requirements during fetal and adult life. We showed that during hematopoietic differentiation, the common lymphoid progenitor is strictly dependent on IL-7 to maintain the B-lineage differentiation potential thus assigning an instructive role of a cytokine in lineage commitment.

T-cell development. In the thymus hematopoietic progenitors give rise to T lymphocytes that can be distinguished by surface marker expression and by function. Thus, T cells expressing a γδ receptor develop from the same type of precursors and we have established that allelic exclusion is obtained by different probabilities of different segments to engage in rearrangement and of different probabilities that a given δ chain has to pair with a γ chain. We are currently investigating the rules underlying lineage commitment of γδ versus αβ expressing T cells. In the thymus, another T cell subset of regulatory T cells is generated. We have shown that neonatal thymectomy, that results in a variable degree of autoimmune disease, does not lead to an absence of regulatory T cells and therefore that they are produced in the thymus before the third day of post-natal life. The physiology and the generation of these cells that regulate homeostasis and autoimmune disease are being studied.

cumano.jpg

Figure. Newly generated hematopoietic stem cells emerging from the ventral aspect of the aorta.



  Web Site

More informations on our web site


  Publications

Publications 2006 of the unit on Pasteur's references database




Activity Reports 2006 - Institut Pasteur
If you have problems with this Web page, please write to rescom@pasteur.fr