Clonal expansion under the microscope: Studying lymphocyte activation and differentiation using live-cell imaging

Michal Polonsky, Benjamin Chain, Nir Friedman*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

18 Scopus citations

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.

Original languageAmerican English
Pages (from-to)242-249
Number of pages8
JournalImmunology and Cell Biology
Volume94
Issue number3
DOIs
StatePublished - 1 Mar 2016
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2016 Australasian Society for Immunology Inc. All rights reserved.

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