Lymphoid Development


Lymphocytes, which are white blood cells, comprise a fundamentally important compartment of the immune system since they are key players in controlling how specific and effective an immune response is to infectious microbes or foreign agents. Lymphocytes exist as three distinct cell lineages, namely Bursa‐derived lymphocytes (B cells), thymus‐derived lymphocytes (T cells) and innate lymphoid cells (ILCs). While B cells and T cells mediate antigen‐specific or adaptive immunity, ILCs mediate preformed or innate immunity. This review discusses the development of B cells, T cells and specifically NK cells, a type of ILC. It details the localisation of development, the selection process these cells face and modifications they may undergo throughout their maturation and localisation to other tissues. The modifications described include functional changes as well as changes in the expression of intracellular and surface molecular markers.

Key Concepts:

  • As proponents of the adaptive immune response, each B cell and T cell express a single unique antigen‐specific receptor providing the host with a large spectrum of specificities, also known as a repertoire.

  • B and T cells must be eliminated during their selection process or selected to develop further into a more specialized immune regulatory cell to avoid autoreactivity.

  • B cell lymphopoiesis is largely confined to the bone marrow and is defined cell size, immunoglobulin gene rearrangement status, activity of transcription factors and expression of cell surface molecules.

  • Peripheral tolerance mechanisms ensure that B cells which survived central tolerance mechanisms become anergic or unresponsive upon encounter of self‐antigen in the periphery.

  • T cell development in the thymus is highly regulated as the developing T cell progenitor moves through the specialized thymic niches and interacts with resident thymic stromal cells, including cortical thymic epithelial cells (cTECs), medullary TECs (mTECs), fibroblasts, dendritic cells and other haematopoietically derived stroma cells.

  • During development in the thymus, T cells undergo both positive and negative selection to eliminate potentially self‐reactive cells.

  • The thymus also promotes the selection of naturally occurring regulatory T cells, namely NK T cells, CD8aa+ intraepithelial (nIEL) T cells, regulatory T (nTreg) cells and IL‐17 producing T (nTh17) cells, which can actively suppress self‐reactive T cells.

  • NK cells are important for host defence against malignantly transformed and virally infected cells and against some bacterial and parasitic infections.

  • NK cells are regulated by signalling downstream of activating and inhibitory germline encoded receptors.

  • NK cells undergo an education process to insure self‐tolerance.

Keywords: lymphocytes; B cells; T cells; innate lymphoid cells; natural killer (NK) cells; common lymphoid progenitor; receptor rearrangement; thymocyte selection; regulatory T cells; NK cell licensing

Figure 1.

Schematic depiction of B cell development. See text for details.

Figure 2.

Schematic depiction of T cell development in the thymus. See text for details.

Figure 3.

Schematic depiction of transcription factors and key surface markers in NK cell development. Peripheral blood NK cells develop from a bone marrow HSC via a CLP intermediate. Surface markers and transcription factors expressed by NK cells at different stages of maturity are indicated.



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Collazo, Michelle M, Gumbleton, Matthew, and Kerr, William G(Jul 2014) Lymphoid Development. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0000902.pub3]