Published Online: 19 APR 2010
Copyright © 2001 John Wiley & Sons, Ltd. All rights reserved.
How to Cite
Zhang, Y. 2010. Lymphocyte Development. eLS.
- Published Online: 19 APR 2010
Like haematopoietic cells of other lineages, both B and T lymphocytes arise from haematopoietic stem cells. Although B-cell development takes place in the bone marrow, T cells are generated in the thymus. With the support of specialised micro-environmental milieus, the progenitors unfold intrinsic genetic programs and progress through multiple intermediate stages to develop into antigen-responsive lymphocytes. A constant theme during this process is lineage diversification. The role of several critical factors has been revealed in recent years, including that of transcription factor Pax5 (paired box 5) and Notch1 signal in B- and T-lineage specification and commitment. In addition, lymphoid development is characterised by somatic recombination of the genes encoding antigen receptors. Such a process ensures the generation of an extremely diversified repertoire of antigen receptors. This newly generated repertoire is then subjected to strict selection before being added to the peripheral pool of mature lymphocytes.
The differentiation from haematopoietic stem cells to antigen-responsive mature lymphocytes is accompanied by sequential changes in gene expression and orderly rearrangements of the genes encoding antigen receptors.
Division of the lymphoid developmental pathways into multiple stages provides a useful framework to dissect the cellular and molecular mechanisms of cell differentiation. But it should be recognised that the transition from one stage to the next is not necessarily as sharp as implied in the diagram.
Lineage specification and commitment is a protracted process, during which cells destined for one lineage does not lose potentials for alternative lineages until relatively late. It is always important to distinguish potential from predominant cell fate.
Cells at different developmental stages are associated with specialised micro-environmental niches, and migration in and out of these niches is essential for the orderly progression of differentiation.
The micro-environmental milieus either determine the fate to be adopted by a progenitor or provide signals to allow cell-intrinsic developmental programs to progress.
Lymphocyte development is an expensive process for the host as the majority of the developing cells die by apoptosis as the result of selection against cells with nonproductively rearranged antigen receptor genes, cells incapable of recognising self-MHC, or cells reactive to self-antigens.
The quantitative differences in signal strength have a remarkable impact on fate choice by developing lymphocytes, such as positive-versus-negative selection, αβ-versus-γδ-lineage diversification, CD4-versus-CD8-lineage decision and Treg cell development.
- T cell;
- B cell;
- lineage commitment;
- gene rearrangement;
- negative selection;
- positive selection