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Born 1953 Email: antonius.rolink@unibas.ch |
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Past Research The research of the Rolink laboratory was and is to a large extent focused on developmental aspects of the immune system. Over the years they have been able to dissect B cell development in mouse and man into various discrete stages based marker expression, rearrangement status of immunoglobulin heavy and light chain loci and cell cycle status. In the early nineties they developed a culture system that allows a very detailed analysis of B cell development in vitro. In collaboration with M. Busslinger and using this culture system they identified the transcription factor Pax5 as the master regulator of B cell development. Thus pro B cells from Pax5 deficient mice are unable to generate B cells. However these pro B cells still possess the capacity to generate various other cells of the hematopoietic lineage including T cells and myeloid cells. More recently they identified the equivalent of this Pax5 deficient pro B cell in the bone marrow of normal mice. Thus early hematopoietic progenitors possess a tremendous developmental plasticity. The Rolink laboratory recently showed that also early T cell progenitors derived from the thymus possess a similar developmental plasticity. |
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Current projects Newly formed B cells generated in the bone marrow have to migrate to spleen to differentiate into mature B cells. The TNF ligand family member BAFF plays a crucial role in this immature - mature B cell transition. Currently a large part of the research in the Rolink laboratory is focused on the role of BAFF and its receptors in late stages of B cell development and peripheral B cell homeostasis. Moreover the potential involvement of deregulated BAFF and/or BAFF receptor expression in development of autoimmunity is addressed. A subset of CD4+ T cells, called regulatory T cells (Tregs), possess immunomodulatory activity. Part of the research in the Rolink laboratory is focused on the developmental aspects of these Tregs. Especially the role of plasmacytoid dendritic in the induction of Treg formation is addressed. Moreover the potential usage of Tregs in therapy of autoimmunity is analyzed. IL-7, Notch and c-kit signaling play an essential role in early lymphocyte development. However very little is known about quantity and the duration requirements of these signals for early lymphocyte development. Part of the research in Rolink laboratory is focused on these two aspects of early T and B cell development. |
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| Research within the Node | |
| Our contribution to C-CPHD will focus on the molecular and functional characterization of early progenitor lymphocytes. We have shown that pro B and pro T cells still possess multi-lineage developmental potential. Upon culturing these progenitors on various stromal cells in the presence of different growth we have been able to differentiate them into B, T, NK and various myeloid cells. We will now determine the gene expression profile of these progenitors and compare those to the expression profiles of the same progenitors differentiating into the various hematopoietic lineages. This analysis should enable to unravel the genetic and epigenetic control of early lymphocyte development. Insights gained from this analysis will be subsequently used to test the importance of specific gene expression patterns and epigenetic mechanisms in lymphocyte development in vivo | |
Schaniel C, Bruno L, Melchers F and Rolink AG. (2002) Multiple hematopoietic cell lineages develop in vivo from transplanted Pax5-deficient pre-B I-cell clones. Blood, 99:472
Balciunaite G, Ceredig R, Massa S and Rolink AG. (2005) A B220+CD117+CD19- hematopoietic progenitor with potent lymphoid and myeloid developmental potential. Eur. J. Immunol., 35:2019.
Balciunaite G, Ceredig R and Rolink AG. (2005) The earliest subpopulation of mouse thymocytes contains potent T, significant macrophage and natural killer cell but no B lymphocyte potential. Blood, 105: 1930.
Ceredig R, Rauch M, Balciunaitr G and Rolink AG. (2006) Increasing Flt3L availability alters composition of a novel bone marrow lymphoid progenitor compartment. Blood, 108:1216.
Ceredig R, Rolink, AG and Brown G. (2009) Models of haematopoiesis: seeing the wood for the trees. Nat. Rev. Immunol., 9:293.