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NR4A Expression by Human Marginal Zone B-Cells
oleh: Kim Doyon-Laliberté, Josiane Chagnon-Choquet, Michelle Byrns, Matheus Aranguren, Meriam Memmi, Pavel Chrobak, John Stagg, Johanne Poudrier, Michel Roger
Format: | Article |
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Diterbitkan: | MDPI AG 2019-10-01 |
Deskripsi
We have previously characterized a human blood CD19<sup>+</sup>CD1c<sup>+</sup>IgM<sup>+</sup>CD27<sup>+</sup>CD21<sup>lo</sup>CD10<sup>+</sup> innate-like B-cell population, which presents features shared by both transitional immature and marginal zone (MZ) B-cells, named herein “precursor-like” MZ B-cells. B-cells with similar attributes have been associated with regulatory potential (Breg). In order to clarify this issue and better characterize this population, we have proceeded to RNA-Seq transcriptome profiling of mature MZ and precursor-like MZ B-cells taken from the blood of healthy donors. We report that ex vivo mature MZ and precursor-like MZ B-cells express transcripts for the immunoregulatory marker CD83 and nuclear receptors NR4A1, 2, and 3, known to be associated with T-cell regulatory (Treg) maintenance and function. Breg associated markers such as CD39 and CD73 were also expressed by both populations. We also show that human blood and tonsillar precursor-like MZ B-cells were the main B-cell population to express elevated levels of CD83 and NR4A1-3 proteins ex vivo and without stimulation. Sorted tonsillar precursor-like MZ B-cells exerted regulatory activity on autologous activated CD4<sup>+</sup> T-cells, and this was affected by a CD83 blocking reagent. We believe these observations shed light on the Breg potential of MZ populations, and identify NR4A1-3 as potential Breg markers, which as for Tregs, may be involved in stabilization of a regulatory status. Since expression and activity of these molecules can be modulated therapeutically, our findings may be useful in strategies aiming at modulation of Breg responses.