lymphocyte progenitors in the thymus and bone marrow differentiate into mature lymphocytes that populate peripheral lymphoid tissues is called lymphocyte development or lymphocyte maturation. The immune repertoire is made up of the collection of antigen receptors— and therefore specificities—expressed by B and T lymphocytes that are produced during the maturation of these cells. Maturation is initiated by signals from cell surface receptors that have two main roles—they promote the proliferation of progenitors and also induce the expression of transcription factors that work together to initiate the rearrangement of specific antigen receptor genes and commit developing cells to a B or a T cell fate. The rearrangement of antigen receptor genes is a key event in the commitment of a progenitor cell to a lym-phoid fate.
We begin this chapter by considering the process of commitment to the B and T lymphocyte lineages and discuss some common principles and mechanisms of B and T cell development. This is followed by a description of the processes that are unique to the maturation of B cells and then of those unique to the development of cells of the T lymphocyte lineage.
OVERVIEW OF LYMPHOCYTE DEVELOPMENT, 173
Commitment to the B and T Cell Lineages and Proliferation of Progenitors, 174
MicroRNAs and Lymphocyte Development, 175 Antigen Receptor Gene Rearrangement and Expression, 176 Selection Processes That Shape the B and T Lymphocyte Repertoires, 176 The Generation of Lymphocyte Subsets, 177
REARRANGEMENT OF ANTIGEN RECEPTOR GENES IN B AND T LYMPHOCYTES, 178
Germline Organization of Ig and TCR Genes, 179
V(D)J Recombination, 181
Generation of Diversity in B and T Cells, 186
B LYMPHOCYTE DEVELOPMENT, 187
Stages of B Lymphocyte Development, 188 Selection of the Mature B Cell Repertoire, 193
MATURATION OF T LYMPHOCYTES, 194
Role of the Thymus in T Cell Maturation, 194 Stages of T Cell Maturation, 195 Selection Processes in the Maturation of MHC-Restricted aß T Cells, 198 y5 T Lymphocytes, 200 NKT Cells, 200
Lymphocytes express highly diverse antigen receptors capable of recognizing a wide variety of foreign substances. This diversity is generated during the development of mature B and T lymphocytes from precursor cells that do not express antigen receptors and cannot recognize and respond to antigens. The process by which
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