ASCT2 (SLC1A5)-Deficient Mice Have Normal B-Cell Development, Proliferation, and Antibody Production

Date

2017

Authors

Masle-Farquhar, Etienne
Bröer, Angelika
Yabas, Mehmet
Enders, Anselm
Bröer, Stefan

Journal Title

Journal ISSN

Volume Title

Publisher

Frontiers Media

Abstract

SLC1A5 (solute carrier family 1, member 5) is a small neutral amino acid exchanger that is upregulated in rapidly proliferating lymphocytes but also in many primary human cancers. Furthermore, cancer cell lines have been shown to require SLC1A5 for their survival in vitro. One of SLC1A5's primary substrates is the immunomodulatory amino acid glutamine, which plays an important role in multiple key processes, such as energy supply, macromolecular synthesis, nucleotide biosynthesis, redox homeostasis, and resistance against oxidative stress. These processes are also essential to immune cells, including neutrophils, macrophages, B and T lymphocytes. We show here that mice with a stop codon in Slc1a5 have reduced glutamine uptake in activated lymphocytes and primary fibroblasts. B and T cell populations and maturation in resting mice were not affected by absence of SLC1A5. Antibody production in resting and immunized mice and the germinal center response to immunization were also found to be normal. SLC1A5 has been recently described as a novel target for the treatment of a variety of cancers, and our results indicate that inhibition of SLC1A5 in cancer therapy may be tolerated well by the immune system of cancer patients.

Description

Keywords

asct2, b cells, slc1a5, glutamine, glutamine uptake, glutaminolysis

Citation

Source

Frontiers in immunology

Type

Journal article

Book Title

Entity type

Access Statement

Open Access

License Rights

DOI

10.3389/fimmu.2017.00549

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