The regulation of lymphocyte activation and proliferation

• Published in: Current opinion in immunology Vol. 51; pp. 32 - 38
• Main Authors: Heinzel, Susanne, Marchingo, Julia M, Horton, Miles B, Hodgkin, Philip D
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.04.2018
• Subjects: Animals; Cell Differentiation - genetics; Cell Differentiation - immunology; Cell Survival; Clonal Evolution - genetics; Clonal Evolution - immunology; Clonal Selection, Antigen-Mediated - genetics; Clonal Selection, Antigen-Mediated - immunology; Gene Expression Regulation, Developmental; Humans; Immunity; Lymphocyte Activation - genetics; Lymphocyte Activation - immunology; Lymphocytes - cytology; Lymphocytes - immunology; Lymphocytes - metabolism; Signal Transduction
• ISSN: 0952-7915; 1879-0372; 1879-0372
• DOI: 10.1016/j.coi.2018.01.002

•Activation induces a programmed timed division burst before return to quiescence.•Clonal integration of activation signals, stochastic probabilities and ongoing signals.•Signals are integrated by each cell in a cumulative manner.•Clonal inheritance and interclonal variation shape the response. Activation induced proliferation and clonal expansion of antigen specific lymphocytes is a hallmark of the adaptive immune response to pathogens. Recent studies identify two distinct control phases. In the first T and B lymphocytes integrate antigen and additional costimuli to motivate a programmed proliferative burst that ceases with a return to cell quiescence and eventual death. This proliferative burst is autonomously timed, ensuring an appropriate response magnitude whilst preventing uncontrolled expansion. This initial response is subject to further modification and extension by a range of signals that modify, expand and direct the emergence of a rich array of new cell types. Thus, both robust clonal expansion of a small number of antigen specific T cells, and the concurrent emergence of extensive cellular diversity, confers immunity to a vast array of different pathogens. The in vivo response to a given pathogen is made up by the sum of all responding clones and is reproducible and pathogen specific. Thus, a precise description of the regulatory principles governing lymphocyte proliferation, differentiation and survival is essential to a unified understanding of the immune system.