[From stem cells to lymphocytes]

Abstract

Two types of pluripotent stem cells form the origins of the cells of the innate and the adaptive immune system, as well as of essential elements of cooperating environments of this system. Pluripotent hematopoietic stem cells and their subordinated, sub-specialized progenitor cells develop, throughout life, the red cells, platelets, myeloid and lymphoid cells of this continuously regenerating cell system. Pluripotent mesenchymal cells generate, among other types of differentiated cells, chondrocytes, epithelial cells, adipocytes and osteoblasts. These osteoblasts not only produce bone, the primary location for the hematopoietic cell development, but also directly interact with the hematopoietic stem and progenitor cells - and also with the mature, antigen-experienced memory types of lymphocytes which return after successful fights with antigens to the place of their origin. These interactions occur both by cell-cell contacts and cytokine-cytokine receptor recognitions in so-called"niches", and induce and guide the developments of the hematopoietic cells. These early phases of hematopoietic development are antigen-independent, because the cells of the adaptive system, the lymphocytes, have not yet made antigen-specific receptors. As soon as these cells express T-cell and B-cell receptors for antigen they are subjected to negative and positive selection pressures, first by auto-antigens in the primary lymphoid organs, then after maturation and migration to secondary lymphoid organs, also to external, foreign antigens. The repertoires of these lymphocytes expressing TcR and BcR adapt to the body's own, as well as external environmental, antigens. While cell-cell contacts with cooperating non-hematopoietic as well as hematopoietic cells, and cytokine-cytokine receptor interactions continue to induce the cellular responses resulting in proliferation, differentiation and/or programmed cell death (apoptosis) of the mature hematopoietic cells, such responses of lymphocytes are now dominated by the specific interactions of their antigen-specific receptors, TcRs or BrCs with antigens.