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Participation of the spleen in the IgA immune response in the gut.

ABSTRACT: The role of the spleen in the induction of an immune response to orally administered antigens is still under discussion. Although it is well known that after oral antigen administration specific germinal centres are not only formed in the Peyers patches (PP) and the mesenteric lymph nodes (mLN) but also in the spleen, there is still a lack of functional data showing a direct involvement of splenic B cells in an IgA immune response in the gut. In addition, after removal of mLN a high level of IgA+ B cells was observed in the gut. Therefore, in this study we analysed the role of the spleen in the induction of IgA+ B cells in the gut after mice were orally challenged with antigens. Here we have shown that antigen specific splenic IgM+ B cells after in vitro antigen stimulation as well as oral immunisation of donor mice were able to migrate into the gut of recipient mice, where they predominantly switch to IgA+ plasma cells. Furthermore, stimulation of recipient mice by orally administered antigens enhanced the migration of the splenic B cells into the gut as well as their switch to IgA+ plasma cells. Removal of the mLN led to a higher activation level of the splenic B cells. Altogether, our results imply that splenic IgM+ B cells migrate in the intestinal lamina propria, where they differentiate into IgA+ plasma cells and subsequently proliferate. In conclusion, we demonstrated that the spleen plays a major role in the gut immune response serving as a reservoir of immune cells that migrate to the site of antigen entrance.

SUBMITTER: Weiberg D

PROVIDER: S-EPMC6171922 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:The spleen is an important site for extramedullary hematopoiesis and tumor immunotolerance. Spleen weight varies with tumor progression and may be a predictor of tumor recurrence. However, to the best of our knowledge, the association between spleen weight and tumor progression remains unclear. The present study revealed a novel role for the spleen in predicting the cellular immune response in tumor-bearing mice. A murine H22 subcutaneous hepatoma model was established. The spleen weight and tumor weight were measured. The proportion of immune cells in peripheral blood and spleen were detected by flow cytometry. The results demonstrated that the spleen weight of tumor-bearing mice at day 21 was higher than that of the controls. In addition, spleen weight was identified to be positively correlated with tumor weight. The percentages of CD4+ and CD8+ T lymphocytes in the spleen were decreased at day 21 after tumor cell inoculation, while those of monocytic-like myeloid-derived suppressor cells (M-MDSCs) and CD11b+F4/80+ macrophages were increased at day 21 after tumor cell inoculation. Similarly, the percentage of polymorphonuclear-like MDSCs (PMN-MDSCs) in the spleen of tumor-bearing mice was increased at days 7, 14 and 21 after tumor cell inoculation. Notably, spleen weight was negatively correlated with the percentages of CD4+ and CD8+ T lymphocytes in the spleen, although spleen and tumor weight were positively correlated with the percentages of M-MDSCs and PMN-MDSCs in the spleen. Similarly, the percentages of CD8+ T lymphocytes in the peripheral blood were decreased, and programmed cell death protein 1 expression on CD8+ T lymphocytes was increased at day 21 after tumor cell inoculation. Furthermore, the percentages of M-MDSCs were increased at day 21 and PMN-MDSCs in the peripheral blood were increased at days 7, 14 and 21 after tumor cell inoculation. Additionally, spleen and tumor weight were also positively correlated with the percentages of M-MDSC and PMN-MDSCs in the peripheral blood of tumor-bearing mice. Collectively, the findings of the present study suggested that spleen weight may be a predictor of tumor prognosis, since it was directly correlated with tumor weight and the percentages of M-MDSC and PMN-MDSCs in tumor-bearing mice.

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Participation of the spleen in the IgA immune response in the gut.

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