Clonal expansion under the microscope: studying lymphocyte activation and differentiation using live‐cell imaging. Issue 3 (22nd December 2015)

• Record Type: Journal Article
• Authors: Polonsky, Michal; Chain, Benjamin; Friedman, Nir
• Is Part Of: Immunology and cell biology. Volume 94:Issue 3(2016)
• Page Start: 242
• Page End: 249
• Publication Date: 2015-12-22
• Subjects: Immunology -- Periodicals; Cytology -- Periodicals; 616.079
• DOI: 10.1038/icb.2015.104
• Languages: English
• ISSNs: 0818-9641

Abstract

Abstract : Clonal expansion of lymphocytes is a hallmark of vertebrate adaptive immunity. A small number of precursor cells that recognize a specific antigen proliferate into expanded clones, differentiate and acquire various effector and memory phenotypes, which promote effective immune responses. Recent studies establish a large degree of heterogeneity in the level of expansion and in cell state between and within expanding clones. Studying these processes in vivo, while providing insightful information on the level of heterogeneity, is challenging due to the complex microenvironment and the inability to continuously track individual cells over extended periods of time. Live cell imaging of ex vivo cultures within micro fabricated arrays provides an attractive methodology for studying clonal expansion. These experiments facilitate continuous acquisition of a large number of parameters on cell number, proliferation, death and differentiation state, with single‐cell resolution on thousands of expanding clones that grow within controlled environments. Such data can reveal stochastic and instructive mechanisms that contribute to observed heterogeneity and elucidate the sequential order of differentiation events. Intercellular interactions can also be studied within these arrays by following responses of a controlled number of interacting cells, all trapped within the same microwell. Here we describe implementations of live‐cell imaging within microwell arrays for studies of lymphocyte clonal expansion, portray insights already gained from these experiments and outline directions for future research. These tools, together with in vivo experiments tracking single‐cell responses, will expand our understanding of adaptive immunity and the ways by which it can be manipulated. Abstract : The March 2016 issue contains a Special Feature on Cutting‐edge single‐cell genomics and modelling in immunology. The recent advent of single‐cell genomics has offered unprecedented possibilities for hypothesis‐independent characterization of cellular heterogeneity and regulatory states. At the same time, the vast datasets produced by these techniques have highlighted the need for new bioinformatics tools to utilize the contained information to the fullest. In this Special Feature, both the experimental methods for producing such data as well as selected modelling approaches are reviewed, with focus on the applications on the study of the immune system. Immunology and Cell Biology thanks the coordinators of this Special Feature ‐ Tapio Lönnberg and Valentina Proserpio ‐ for their planning and input.