Journal
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
Volume 138, Issue 4, Pages 1170-+Publisher
MOSBY-ELSEVIER
DOI: 10.1016/j.jaci.2015.12.1319
Keywords
Rodent; B cells; autoimmunity; IL-10; marginal zone B cell; B1 B cell; phosphatidylinositol 3-kinase; phosphatase and tensin homolog; regulatory B cell
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Funding
- Ministry of Education, Science, and Culture of Japan [23791260]
- Ministry of Education, Science, and Culture of Japan
- Japanese Government
- Grants-in-Aid for Scientific Research [15H02361, 26290038, 15H01509] Funding Source: KAKEN
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Background: IL-10-producing regulatory B (B10) cells potently suppress allergic diseases, such as contact hypersensitivity (CHS). Splenic B10 cells share overlapping phenotypic markers with CD5(+) B1 B cells, CD1d(hi) CD21(+) CD23(-) marginal zone (MZ) B cells, and CD1d(hi) CD21(+) CD23(+) T2-MZ precursor B cells but do not exclusively belong to either subset. Objective: In this study we investigated the signaling mechanisms and a novel phenotypic parameter of B10 cells. Method: We performed microarray analysis comparing IL-10(+) and IL-10(+) B cells. B cell-specific phosphatase and tensin homolog (PTEN)-deficient mice, which exhibit aberrant activation of the phosphatidylinositol 3-kinase (PI3K)-Akt pathway in B cells, were examined. Results: Microarray analysis revealed that the PI3K-Akt pathway is important for IL-10 production in B cells. PI3K-Akt pathway inhibitors reducedB10 cell numbers invitro. B10 cellnumberswere significantly increased in B cell-specific PTEN-deficient mice. The CHS response was significantly diminished in PTEN-deficient mice. Unexpectedly, splenic B10 cells in these mice were found within the B1 B-cell subset but not within the MZ B-cell subset. In wild-type mice not only MZ B10 cells but also B1-B10 cells were identified in the spleen. In addition, these 2 B10 cell subsets were predominantly found within the CD9(+) CD80(+) B-cell fraction. Conclusion: A novel splenic B1 regulatory cell subset (B1-B10 cells) was identified. Our findings show that the PI3K-Akt pathway in B cells is critical for B10 cell development and CHS response and that CD9/CD80 coexpression is a novel phenotypic parameter for both MZ-B10 and B1-B10 cells.
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