B cell activation and proliferation increase intracellular zinc levels

Johanna Ollig,Veronika Kloubert,Kathryn M Taylor,Lothar Rink

doi:10.1016/j.jnutbio.2018.10.008

Johanna Ollig, Veronika Kloubert + Show 2 more

Open Access

https://doi.org/10.1016/j.jnutbio.2018.10.008

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Abstract

Zinc ions serve as second messengers in major cellular pathways, including the regulation pathways of proliferation and their proper regulation is necessary for homeostasis and a healthy organism. Accordingly, expression of zinc transporters can be altered in various cancer cell lines and is often involved in producing elevated intracellular zinc levels. In this study, human B cells were infected with Epstein–Barr virus (EBV) to generate immortalized cells, which revealed traits of tumor cells, such as high proliferation rates and an extended lifespan. These cells showed differentially altered zinc transporter expression with ZIP7 RNA and protein expression being especially increased as well as a corresponding increased phosphorylation of ZIP7 in EBV-transformed B cells. Accordingly, free zinc levels were elevated within these cells. To prove whether the observed changes resulted from immortalization or rather high proliferation, free zinc levels in in vitro activated B cells and in freshly isolated B cells expressing the activation marker CD69 were determined. Here, comparatively increased zinc levels were found, suggesting that activation and proliferation, but not immortalization, act as crucial factors for the elevation of intracellular free zinc.

Highlights

Zinc is an essential trace element and fulfills numerous functions in the human body
The free zinc level in peripheral blood mononuclear cells (PBMC) was not affected by H-LeuLeu-OMe · HBr, which was used for T cell depletion (Fig. 1A)
Alterations of zinc transporters going along with increased zinc levels were previously found in various solid cancer cells, e.g. in invasive breast carcinoma [24] and malignant ovarian tumors [53]

Summary

Introduction

Zinc is an essential trace element and fulfills numerous functions in the human body. Since zinc deficiency was confirmed in 1963 to cause severe effects in humans [1], various researchers have centered their interest on the study of zinc and its effects. The importance of zinc is described especially for the immune system [2]. Zinc deficiency severely affects the immune system, as impressively shown in acrodermatitis enteropathica, an inherited disorder with a loss-of-function mutation of ZIP4 which is accompanied by zinc deficiency [4]. We examined B cells, whose correct function is indispensable for the human immune system. Dietary zinc deficiency leads to lymphopenia by loss of precursor B cells [6].

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