Development of the immune system from stem cells
The senior group will continue to work on some projects which were developed at the Basel Institute for Immunology and which have focused on the development of cells of the innate and adaptive from stem cells and early progenitors and which have studied the development of B-lymphocytes in greater details.
Stem cells of the adaptive and the innate immune system
All cells of the innate and adaptive immune system can originate from a single pluripotent hematopoietic cell (pHSC). pHSC are characterized by at least three properties. Firstly, upon differentiation in an appropriate environment they can give rise to cells of the erythroid, megakaryocytic, myeloid and lymphoid lineages. This capacity has been experimentally documented by in vivo transplantation into hematopoietically deficient, e.g. lethally irradiated hosts, or by in vitro differentiation under appropriate tissue culture conditions. Secondly, after division, in vivo or in vitro, pHSC are expected to retain their pluripotent stem cell property in at least one of the two daughter cells, i.e. they have the capacity of self renewal. pHSC are expected to have an extended proliferative capacity of this kind. Thirdly, upon transplantation, pHSC are able to home back to heir appropriate sites in the bone marrow, from where they can be re-isolated and replanted into secondary recipients without loss of their three stem cell properties [1-12]. If the rates of repopulations into the different hematopoietic lineages are appropriate and rapid enough, stem cells can protect lethally irradiated recipients from death.
Development of B lymphocytes from progenitor and precursor cells can be followed by the stepwise rearrangements of the V, D and J segments of the immunoglobulin (Ig) heavy (H) and light (L) chain gene loci, by differential expression of specific genes with functions in this developmental pathway, by differential growth properties of cells in this development 'in vitro', and by differential properties to populate B lymphocyte- precursor and -mature cell compartments in recipient mice upon transplantation (for reviews see [13, 14]). B cell development from early progenitors and precursors to mature, surface Ig-expressing (sIg+) B cells can be induced and followed 'in vitro' , as well as 'in vivo' after transplantation into severe- combined immunodeficiency (SCID) or RAG-/- mice. 'In vivo', the transplantation of proB or preB-I cells leads to a long-term population of some of the mature B cell compartments [16, 17].