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PLoS One. 2014 Jan 17;9(1):e83575. doi: 10.1371/journal.pone.0083575. eCollection 2014.

Involvement of suppressive B-lymphocytes in the mechanism of tolerogenic dendritic cell reversal of type 1 diabetes in NOD mice.

Author information

1
Division of Immunogenetics, Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States of America ; RiMed Foundation, Palermo, Italy.
2
Penn State University Hershey Medical Center, Hershey, Pennsylvania, United States of America.
3
Division of Immunogenetics, Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States of America.
4
Division of Immunogenetics, Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States of America ; Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States of America.

Abstract

The objective of the study was to identify immune cell populations, in addition to Foxp3+ T-regulatory cells, that participate in the mechanisms of action of tolerogenic dendritic cells shown to prevent and reverse type 1 diabetes in the Non-Obese Diabetic (NOD) mouse strain. Co-culture experiments using tolerogenic dendritic cells and B-cells from NOD as well as transgenic interleukin-10 promoter-reporter mice along with transfer of tolerogenic dendritic cells and CD19+ B-cells into NOD and transgenic mice, showed that these dendritic cells increased the frequency and numbers of interleukin-10-expressing B-cells in vitro and in vivo. The expansion of these cells was a consequence of both the proliferation of pre-existing interleukin-10-expressing B-lymphocytes and the conversion of CD19+ B-lymphcytes into interleukin-10-expressing cells. The tolerogenic dendritic cells did not affect the suppressive activity of these B-cells. Furthermore, we discovered that the suppressive murine B-lymphocytes expressed receptors for retinoic acid which is produced by the tolerogenic dendritic cells. These data assist in identifying the nature of the B-cell population increased in response to the tolerogenic dendritic cells in a clinical trial and also validate very recent findings demonstrating a mechanistic link between human tolerogenic dendritic cells and immunosuppressive regulatory B-cells.

PMID:
24465383
PMCID:
PMC3894962
DOI:
10.1371/journal.pone.0083575
[Indexed for MEDLINE]
Free PMC Article
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