Activated naïve B cells promote development of malignant pleural effusion by differential regulation of T H 1 and T H 17 response.

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 naive 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 T(H)17 cells were present in B cell-deficient mouse MPH, which paralleled to the reduced MPH volume and longer survival time. Adoptive transfer of activated naive B cells into B cell-deficient mice was able to increase T(H)1 cells and decrease T(H)17 cells in MPE and shorten the survival of mice bearing MPE. Furthermore, we demonstrated that activated naive B cells inhibited T(H)17-cell expansion via the PD-1/PD-L1 pathway and promoted naive CD4(+) T-cell differentiation into T(H)1/T(H)17 cells through secreting IL-27/1L-6 independent of the PD-1/PD-L1 pathway. Collectively, our data uncovered a mechanism by which naive B cells promote MPE formation by regulating T(H)1/T(H)17 cell responses, making these B cells an attractive target for therapeutic intervention in the fight against cancer.