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NR4A Expression by Human Marginal Zone B-Cells.

Kim Doyon-Laliberté1,2, Josiane Chagnon-Choquet3,4, Michelle Byrns5,6

  • 1Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Tour Viger 900 rue St-Denis, Montréal, QC H2X 0A9, Canada. k.doyonlaliberte@videotron.ca.

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Summary
This summary is machine-generated.

We identified a novel human B-cell population, precursor-like marginal zone (MZ) B-cells, that exhibits regulatory potential (Breg). These cells express key immunoregulatory markers like CD83 and NR4A1-3, suggesting a role in immune modulation.

Keywords:
B regulatory cellsNR4Ahuman marginal zone B-cells

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Area of Science:

  • Immunology
  • Cell Biology

Background:

  • A distinct human blood B-cell population, termed "precursor-like" marginal zone (MZ) B-cells, shares characteristics with transitional immature and MZ B-cells.
  • This population has been anecdotally linked to regulatory B-cell (Breg) functions.

Purpose of the Study:

  • To comprehensively characterize the immunoregulatory potential of precursor-like MZ B-cells.
  • To identify molecular markers associated with the regulatory function of these B-cells.

Main Methods:

  • RNA-sequencing (RNA-Seq) transcriptome profiling of mature MZ and precursor-like MZ B-cells from healthy donors.
  • Quantitative analysis of immunoregulatory marker expression (CD83, NR4A1-3, CD39, CD73) on B-cell populations.
  • Functional assays assessing the regulatory activity of sorted precursor-like MZ B-cells on autologous CD4+ T-cells, including blockade studies with CD83 reagents.

Main Results:

  • Both mature and precursor-like MZ B-cells express CD83 and nuclear receptors NR4A1, 2, and 3, which are linked to T-regulatory cell (Treg) function.
  • CD39 and CD73, known Breg markers, were also expressed by these B-cell subsets.
  • Precursor-like MZ B-cells, particularly from tonsils, showed elevated ex vivo expression of CD83 and NR4A1-3 proteins without stimulation.
  • Sorted tonsillar precursor-like MZ B-cells demonstrated regulatory activity on activated CD4+ T-cells, which was sensitive to CD83 blockade.

Conclusions:

  • Precursor-like MZ B-cells possess significant regulatory potential (Breg).
  • NR4A1-3 nuclear receptors are identified as potential novel Breg markers, potentially involved in stabilizing regulatory status, analogous to Tregs.
  • These findings offer insights into Breg cell biology and suggest therapeutic strategies targeting Breg responses through modulation of these identified markers.