Alacrity of Cells Engaged in the Immune Response

Abstract

A hypothesis is postulated and experimental findings are given that a special kind of cell heterogeneity exists that renders cells differentially sensitive to the epitopal stimulus with the consequence that only a portion of ligand‐specific cells engages in the response. The differential sensitivity is based on epigenetically driven cell‐to‐cell variations in the expressed gene products, such that every cell becomes unique in its molecular profile, and will preserve its individuality in ‘sensing’ the boundary conditions of the response milieu. The readiness of cells to engage in the response will be termed alacrity. High‐alacrity cells are ready to respond under given conditions because their molecular expression pattern – both in qualitative and in quantitative terms – matches the response milieu. This heterogeneity has little to do with the BCR and TCR specificity, that is, not all antigen‐specific cells respond to a stimulus, and cells failing to respond do so because their overall molecular pattern is inadequate to the conditions of the response milieu. The corollary to this proposition is that whatever physiological conditions prevail, some ligand‐specific cells will likely be ready to engage in the response, because their uniqueness makes them differentially reactive to external signals. Although the pool of cells available for any response is restricted under any given boundary condition, some idle cells are saved to be ‘in reserve’. Experiments are described that are compatible with this proposition, and approaches are suggested to elucidate the mechanism of developing and maintaining alacrity. This paper is a contribution to the Centennial conference in honour of Niels Kaj Jerne, held in Lisbon November 2011.