Skip to Main Content

Lymphopoiesis refers to the process by which the cellular components of the immune system (i.e., T cells, B cells, and natural killer cells, and certain dendritic cells) are produced during hematopoietic differentiation. This process begins with the hematopoietic stem cell and continues through progenitor stages down a series of mostly diverging lineage pathways, ultimately resulting in the remarkable diversity and flexibility of the immune system. Although the more terminal events in lymphocyte differentiation and function have been defined in detail (see Chaps. 77, 78, and 79), the earliest events during which hematopoietic stem cells undergo lymphoid lineage commitment are less-well understood and still somewhat controversial. Although the conceptual framework for the questions of lymphoid commitment has been established largely on studies in murine species, experimental systems now exist to better understand how such events are controlled in humans. This chapter summarizes what is known about the ontogeny of lymphoid development and the control of lymphoid differentiation and discusses some of the persisting controversies in the field.

Acronyms and Abbreviations

Acronyms and abbreviations that appear in this chapter include: B, bone marrow derived; BCR, B-cell receptor; CLP, common lymphoid progenitor; E, days of gestation; EBF, early B-cell factor; HSC, hematopoietic stem cell; Ig, immunoglobulin; IL, interleukin; LMPP, lymphoid-multipotential primed progenitor; LSK, linnegsca-1+c-kit+; NK, natural killer; SCID, severe combined immunodeficiency.

Blood is formed from a succession of sites during embryonic and fetal development, beginning outside the embryo in the yolk sac. Soon afterward, hematopoiesis begins in the embryo proper, initially in the paraaortic splanchnopleure (PAS), and aorto-gonad-mesonephros (AGM) regions, then the fetal liver, spleen, and finally the fetal marrow (see Chap. 6). With each change of anatomical site the range of hematopoiesis becomes progressively more complex and similar to that of the adult (Fig. 76–1).

Figure 76–1.

Timing of lymphohematopoiesis during prenatal development. Shown is the timeline for activity in each site of hematopoiesis in the embryo and fetus of (A) human and (B) mouse. Solid lines show tissues in which long-term reconstituting, multilineage definitive hematopoietic stem cells (HSCs) are present. Open lines show sites where only more differentiated hematopoietic cells are present (i.e., HSCs are absent), e.g., myeloid and erythroid cells in yolk sac, thymocytes in thymus. “B- and T-cell potential” (in ovals) refers to the presence of progenitor cells in the paraaortic splanchnopleure (PAS) that can generate T- and B-lymphoid cells when cultured in vitro. B and T cells are first detected in vivo in fetal liver and thymus, respectively, at times shown in rectangles. Not shown here are other sites of hematopoiesis such as omentum, placenta, and spleen, in which exact onset of human lymphoid potential is less clear. AGM, aorto-gonad-mesonephros.

When assigning hematopoietic function to each developmental stage, it is important to distinguish the lineage ...

Pop-up div Successfully Displayed

This div only appears when the trigger link is hovered over. Otherwise it is hidden from view.