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Dr. Antonius G. Rolink

 
 

Dr. Antonius G. Rolink
Developmental and Molecular Immunology
Department of Biomedicine
University of Basel
Mattenstrasse 28
4058 - Basel / Switzerland

 
E-mail

antonius.rolink@unibas.ch

Phone +41 61 267 16 31
Fax +41 61 695 30 70
 
Homepage
 
 
 
 
Antonius G. Rolink is Professor of Immunology at the University of Basel. His research focus is the understanding of the molecular mechanisms guiding mouse lymphocyte development. Haematopoietic stem cells (HSCs), a very rare bone marrow cell type, are responsible for the life-long production of all blood cells including T and B lymphocytes. Until recently, it was thought that the differentiation of HSCs into the various haematopoietic cells was a rather hierarchical process with differentiation along a particular lineage associated with a progressive loss of potential of generating other lineages. However, the finding that pro B cells from the transcription factor Pax5 deficient mouse possess the potential to give rise various hematopoietic lineages including myeloid cells have challenged this idea for the first time. Moreover, the recent development of very sensitive and quantitative in vitro assays, together with the identification of new progenitor subpopulations, has challenged this idea even further. Thus, we have identified in the mouse bone marrow a novel population of cells, representing 0.2% of all nucleated cells, which, can differentiate in vitro into B and T lymphocytes, as well as myeloid cells. Based on these findings, we have called these cells “early progenitors with lymphoid and myeloid developmental potential”, or EPLM. Currently we studying the molecular mechanisms that guide the development of EPLM into T and B cells using the various in vitro and in vivo systems that we have established. Yet another research focus of our laboratory is the unraveling of the mechanisms that guide the development of the human hematopoietic system. Therefore we have established a so-called humanized mouse model. Thus, upon transplantation with human CD34+ cord blood stem cells, newborn RAG-2/gc mice show a robust and long-lasting reconstitution of the primary and secondary lymphoid organs by progenitor and mature human lymphocytes. Currently, we are using this model system to analyze the molecular mechanisms underlying human lymphocyte development. Our group is also interested the mechanisms that guide regulatory T cell formation and moreover we analyze the therapeutic potential of these cells in various disease models.

For additional information, see http://biomedizin.unibas.ch/nc/about-us/people/profil/profile/person/rolink/

 
Recent publications related to stem cells:

  • Swee LK, Tardivel A, Schneider P. and Rolink A. (2010). Rescue of the mature B cell compartment in BAFF-deficient mice by treatment with recombinant Fc-BAFF. Immunol Lett. 131:40-8.
     
  • Bosco N, Swee LK, Bénard A, Ceredig R. and Rolink A. (2010). Auto-reconstitution of the T-cell compartment by radioresistant hematopoietic cells following lethal irradiation and bone marrow transplantation. Exp Hematol. 38:222-232.
     
  • Tussiwand R, Engdahl C, Gehre N, Bosco N, Ceredig R, Rolink AG. (2011). The preTCR-dependent DN3 to DP transition requires Notch signaling, is improved by CXCL12 signaling and is inhibited by IL-7 signaling. Eur J Immunol. 41:3371-80.
     
  • Tussiwand R, Rauch M, Flück LA, Rolink AG. (2012). BAFF-R expression correlates with positive selection of immature B cells. Eur J Immunol. 42:206-16.
     
  • Vigano MA, Ivanek R, Balwierz P, Berninger P, van Nimwegen E, Karjalainen K, Rolink A. (2014). An epigenetic profile of early T-cell development from multipotent progenitors to committed T-cell descendants. Eur J Immunol. 44:1181-93.
     
  • Tsapogas P, Swee LK, Nusser A, Nuber N, Kreuzaler M, Capoferri G, Rolink H, Ceredig R, Rolink A. (2014). In vivo evidence for an instructive role of fms-like tyrosine kinase-3 (FLT3) ligand in hematopoietic development. Haematologica 99:638-46.
     
  • Swee LK, Nusser A, Curti M, Kreuzaler M, Rolink H, Terracciano L, Melchers F, Andersson J, Rolink A. (2014). The amount of self-antigen determines the effector function of murine T cells escaping negative selection. Eur J Immunol. 44:1299-312.
     
  • von Muenchow L, Engdahl C, Karjalainen K, Rolink AG. (2014). The selection of mature B cells is critically dependent on the expression level of the co-receptor CD19. Immunol Lett. 2014 Jan 25. pii: S0165-2478(14)00015-7. doi: 10.1016/j.imlet.2014.01.011. [Epub ahead of print]
     
  • Nusser A, Nuber N, Wirz OF, Rolink H, Andersson J, Rolink A. (2014). The development of autoimmune features in aging mice is closely associated with alterations of the peripheral CD4⁺ T-cell compartment. Eur J Immunol. 44:2893-902.
     
  • Gehre N, Nusser A, von Muenchow L, Tussiwand R, Engdahl C, Capoferri G, Bosco N, Ceredig R, Rolink AG. (2015). A stromal cell free culture system generates mouse pro-T cells that can reconstitute T-cell compartments in vivo. Eur J Immunol. 45:932-42.
     
  • Manoharan A, Du Roure C, Rolink AG, Matthias P. (2015). De novo DNA Methyltransferases Dnmt3a and Dnmt3b regulate the onset of Igκ light chain rearrangement during early B-cell development. Eur J Immunol. 45:2343-55.
     
  • von Muenchow L, Alberti-Servera L, Klein F, Capoferri G, Finke D, Ceredig R, Rolink A, Tsapogas P. (2016). Permissive roles of cytokines interleukin-7 and Flt3 ligand in mouse B-cell lineage commitment. Proc Natl Acad Sci USA 113:E8122-E8130.
     
  • von Muenchow L, Tsapogas P, Albertí-Servera L, Capoferri G, Doelz M, Rolink H, Bosco N, Ceredig R, Rolink AG. (2017). Pro-B cells propagated in stromal cell-free cultures reconstitute functional B-cell compartments in immunodeficient mice. Eur J Immunol. 47:394-405.

 
Reviews

  • Ceredig R, Rolink AG. and Brown G. (2009). Models of hematopoiesis: seeing the wood for the trees. Nature Rev Immunol. 9:293-300.
     
  • Ceredig R and Rolink AG. (2012). The key role of IL-7 in lymphopoiesis. Semin Immunol. 24:159-64.
     
  • Brown G, Mooney CJ, Alberti-Servera L, Muenchow Lv, Toellner KM, Ceredig R, Rolink A. (2015). Versatility of stem and progenitor cells and the instructive actions of cytokines on hematopoiesis. Crit Rev Clin Lab Sci. 52:168-79.
     
  • Tsapogas P, Mooney CJ, Brown G, Rolink A. (2017). The Cytokine Flt3-Ligand in Normal and Malignant Hematopoiesis. Int J Mol Sci. 18(6).