1. Activated naïve B cells promote development of malignant pleural effusion by differential regulation of T H 1 and T H 17 response.
- Author
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Wu XZ, Shi XY, Zhai K, Yi FS, Wang Z, Wang W, Pei XB, Xu LL, Wang Z, and Shi HZ
- Subjects
- Animals, B-Lymphocytes pathology, Mice, Mice, Knockout, Neoplasm Proteins genetics, Neoplasm Proteins immunology, Pleural Effusion, Malignant genetics, Pleural Effusion, Malignant pathology, Signal Transduction genetics, Th1 Cells pathology, Th17 Cells pathology, B-Lymphocytes immunology, Pleural Effusion, Malignant immunology, Signal Transduction immunology, Th1 Cells immunology, Th17 Cells immunology
- Abstract
Inflammatory signaling networks between tumor cells and immune cells contribute to the development of malignant pleural effusion (MPE). B cells have been found in MPE; however, little is known about their roles there. In the present study, by using mouse MPE models, we noted that although the total B cells in MPE were decreased as compared with the corresponding blood and spleen, the percentage of activated naïve B cells expressing higher levels of CD80, CD86, myosin heavy chain-II, CD44, CD69, and programmed cell death-ligand 1 (PD-L1) molecules were increased in wild-type mouse MPE. Compared with wild-type mice, decreased T helper (T
H )1 cells and increased TH 17 cells were present in B cell-deficient mouse MPE, which paralleled to the reduced MPE volume and longer survival time. Adoptive transfer of activated naïve B cells into B cell-deficient mice was able to increase TH 1 cells and decrease TH 17 cells in MPE and shorten the survival of mice bearing MPE. Furthermore, we demonstrated that activated naïve B cells inhibited TH 17-cell expansion via the PD-1/PD-L1 pathway and promoted naïve CD4+ T-cell differentiation into TH 1/TH 17 cells through secreting IL-27/IL-6 independent of the PD-1/PD-L1 pathway. Collectively, our data uncovered a mechanism by which naïve B cells promote MPE formation by regulating TH 1/TH 17 cell responses, making these B cells an attractive target for therapeutic intervention in the fight against cancer.- Published
- 2018
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