7-25 Inhibitory receptors on lymphocytes downregulate immune responses by recruiting protein or lipid phosphatases.
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The Development of B and T Lymphocytes
The production of new lymphocytes, or lymphopoiesis, takes place in specialized lymphoid tissues—the central (or primary) lymphoid tissues— which are the bone marrow for most B cells and the thymus for most T cells. Precursors for both populations originate in the bone marrow, but whereas B cells complete most of their development there, the precursors of most T cells migrate to the thymus, where they develop into mature T cells. A major goal of lymphopoiesis is to generate a diverse repertoire of B-cell receptors and T-cell receptors on circulating B and T cells, respectively, thereby enabling an individual to make adaptive immune responses against the wide range of pathogens encountered during a lifetime. In the fetus and the juvenile, the central lymphoid tissues are the sources of large numbers of new lymphocytes, which migrate to populate the peripheral lymphoid tissues (also called secondary lymphoid tissues) such as lymph nodes, spleen, and mucosal lymphoid tissue. In mature individuals, the development of new T cells in the thymus slows down, and peripheral T-cell numbers are maintained by the division of mature T cells outside the central lymphoid organs. New B cells, in contrast, are continually produced from the bone marrow, even in adults. This chapter will focus on the development of T cells and B cells from their uncommitted progenitors, with an emphasis on the major populations of CD4+ and CD8+ T cells and B cells. The development of additional subsets of T cells and B cells, such as invariant NKT (iNKT) cells, Treg cells, γ:δ TCR+ T cells, B-1 B cells, and marginal zone B cells will be briefly discussed.
The structure of the antigen-receptor genes expressed by B cells and T cells, and the mechanisms by which a complete antigen receptor is assembled, were described in Chapters 4 and 5. Once an antigen receptor has been formed, rigorous testing is required to select lymphocytes that carry useful antigen receptors—that is, antigen receptors that can recognize a wide spectrum of pathogens and yet will not react against an individual’s own cells. Given the incredible diversity of receptors that the rearrangement process can generate, it is important that those lymphocytes that mature are likely to be useful in recognizing and responding to foreign antigens, especially as an individual can express only a small fraction of the total possible receptor repertoire in his or her lifetime. We describe how the specificity and affinity of the receptor for self ligands are tested to determine whether the immature lymphocyte will either survive and join the mature repertoire, or die. In general, it seems that developing lymphocytes whose receptors interact weakly with self antigens, or that bind self antigens in a particular way, receive a signal that enables them to survive. This process, known as positive selection, is particularly critical in the development of α:β T cells, which recognize composite antigens consisting of peptides bound to MHC molecules, because it ensures that an individual’s T cells will be able to respond to peptides bound to one’s own MHC molecules.