Lymphocytes: Antigen‐Induced Gene Activation

Abstract

Lymphocytes are activated upon antigen (Ag) recognition by their clonotypic surface Ag receptors, TCR in the case of T cells and BCR in the case of B cells. Lymphocyte activation triggers multiple signalling cascades that converge in the cell nucleus to cause significant changes in the pattern of gene expression that determine the phenotype of activated lymphocytes and, ultimately, the type of immune response. Primary activation in T cells is coupled to rapid T‐cell cycling and progressive epigenetic changes that guide the cell down distinct T‐cell lineages, either effector (TH1, TH2, TH17) or regulatory (Treg), characterised by the expression of specific transcription factors and cytokines. CD8 T cells and B cells also differentiate into cytotoxic thymus‐derived lymphocytes and plasma cells, respectively, driven by specific activation in the context of CD4 TH cells (helper) and the cytokine microenvironment.

Key Concepts:

  • Lymphocyte stimulation leads to the activation of selected transcription factors depending on the type of signals.

  • Lymphocyte differentiation and function is directed by specific transcription factors that determine the cell lineage.

  • Interaction and/or collaboration of different transcription factors lead to expression or repression of different genes.

  • Alterations in the control of TFs activity lead to the development of autoimmune diseases and/or other pathologies.

  • Some TFs and the molecular pathways that control their activity are targets for the treatment of different diseases.

Keywords: antigen receptor; lymphocyte activation; signal transduction; transcription factors; cytokines

Figure 1.

Plasticity and function of CD4 T cells. Plasticity of CD4 T helper cells depends on the differentiation state and the TH lineage; that is, at early stages or differentiation, all CD4 T cells can be switched to other lineage. Tregs and TH17 cells maintain plasticity once differentiated; however, TH1 and TH2 lose this property after lineage commitment. TH1 cells collaborate with CD8 T cells for their differentiation into CTLs whereas TH2 cells provide help to B cells that differentiate into plasma cells. Cytokines produced by TH17 cells are proinflammatory and Tregs are immunosupressive.

Figure 2.

Antigen‐induced lymphocyte activation: the two‐signal paradigm. Four major steps take place in lymphocyte activation: Ag recognition and formation of receptor oligomers; activation of signalling pathways; activation and translocation of TFs; and changes in gene expression that characterise activated lymphocytes. In addition, activation of some of the signalling pathways has effects in many other cell processes. For details on specific aspects of T‐ and B‐cell activation, see text.

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Suárez‐Fueyo, Abel, Madrenas, Joaquín, and Criado, Gabriel(Sep 2013) Lymphocytes: Antigen‐Induced Gene Activation. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0001191.pub3]