14 Hematopoietic Stem Cells: Lymphopoiesis and the Problem of Commitment Versus Plasticity

Abstract

B lymphocytes, T lymphocytes, and natural killer (NK) cells (cells of the lymphoid lineages) and erythrocytes, megakaryocytes, platelets, granulocytes, monocytes, macrophages, osteoclasts, and dendritic cells (cells of the erythroid/myeloid lineages) are all descendants of a pluripotent hematopoietic stem cell (pHSC) (for recent reviews, see Fuchs and Segre 2000 and Weissman 2000). In fact, transplantation of a single pHSC can reconstitute a lethally irradiated host with all these lineages of cells. The differentiated cells of the erythroid/myeloid and lymphoid lineages, with the exception of memory B and T cells, turn over rapidly, with half-lives between days and weeks. Therefore, in order to maintain the pools of hematopoietic cells in an individual, these cells have to be continuously generated throughout life by cell division and differentiation from stem cells.

The cells of the adaptive immune system, B and T lymphocytes, rearrange V, D, and J segments during their development to form functional IgH and L-chain genes in B cells, and TCR α, β, γ and δ genes in T cells (Tonegawa 1983). Through positive and negative selection of the original antigen-recognizing repertoires in the primary lymphoid organs, for B cells in the bone marrow, for T cells in the thymus, the repertoires are shaped by selective processes. The selected repertoires of lymphocytes become available for recognition of foreign antigens in the secondary lymphoid organs of the peripheral immune system. These processes of repertoire selection must continue to operate throughout life, as lymphocytes continue to be generated from pHSC and from progenitors through...