Diversity of gut microflora is required for the generation of B cell with regulatory properties in a skin graft model
File(s)
Published version
Author(s)
Type
Journal Article
Abstract
B cells have been reported to promote graft rejection through alloantibody production. However, there is growing evidence that B cells can contribute to the maintenance of tolerance. Here, we used a mouse model of MHC-class I mismatched skin transplantation to investigate the contribution of B cells to graft survival. We demonstrate that adoptive transfer of B cells prolongs skin graft survival but only when the B cells were isolated from mice housed in low sterility "conventional" (CV) facilities and not from mice housed in pathogen free facilities (SPF). However, prolongation of skin graft survival was lost when B cells were isolated from IL-10 deficient mice housed in CV facilities. The suppressive function of B cells isolated from mice housed in CV facilities correlated with an anti-inflammatory environment and with the presence of a different gut microflora compared to mice maintained in SPF facilities. Treatment of mice in the CV facility with antibiotics abrogated the regulatory capacity of B cells. Finally, we identified transitional B cells isolated from CV facilities as possessing the regulatory function. These findings demonstrate that B cells, and in particular transitional B cells, can promote prolongation of graft survival, a function dependent on licensing by gut microflora.
Date Issued
2015-06-25
Date Acceptance
2015-05-22
Citation
Scientific Reports, 2015, 5
ISSN
2045-2322
Publisher
Nature Publishing Group
Journal / Book Title
Scientific Reports
Volume
5
Copyright Statement
This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
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Subjects
Adaptive Immunity
Adoptive Transfer
Animals
Anti-Bacterial Agents
B-Lymphocytes
Cytokines
Disease Models, Animal
Gastrointestinal Microbiome
Graft Survival
Histocompatibility Antigens Class I
Immune Tolerance
Interleukin-10
Lipopolysaccharides
Lymph Nodes
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Mice, Knockout
Skin Transplantation
Spleen
Transplantation, Homologous
Publication Status
Published
Article Number
11554