Human pleural B cells regulate IFN-g production by local T and NK cells in Mycobacterium tuberculosis-induced delayed hypersensitivity reaction.

SCHIERLOH P; LANDONI VI; BALBOA L; MUSELLA RM; CASTAGNINO J; MORAÑA E; DE CASADO GS; PALMERO DJ; SASIAIN MC

CLINICAL SCIENCE (LONDON, ENGLAND : 1979)

PORTLAND PRESS LTD

Lugar: Londres; Año: 2014

0143-5221

Delayed type hypersensitivity (DTH) reactions are secondary cellular immune responses, which appear 24-72 hours after antigen exposure. Tuberculous pleurisy is a common manifestation of extrapulmonary tuberculosis (TB) and is considered a human model of TH1-mediated DTH. In order to identify functional cross-talk among cellular populations sited at this inflammatory microenvironment, we analyzed phenotypic and functional features of human B cells isolated from pleural fluid (PF) of TB patients. Freshly isolated PF-B cells displayed a lower expression of CD20, CD1d and HLA-DR, and a higher expression of CD95, CD38, CD25, CXCR3 and CXCR4 than their peripheral blood counterpart, suggesting a non-classical in situ activation. Despite memory PF-T cells frequencies were increased, frequencies of memory PF-B cells were not. We demonstrated that upon stimulation with g-irradiated M. tuberculosis (Mtb), mycobacterial secreted proteins or a lectin mitogen, PF-B cells showed a strong activation and produced IL-10 by a mechanism that was dependent on bystander activation of CD19neg-PF cells. Besides, within PF cells, B cells diminished in vitro Mtb-induced IFN-γ production by T and NK cells in an IL-10-dependent manner. Finally, we found that the lower the frequency of B cells, the higher the ratio of IFN-γ/IL-10 within PF. Thus, our results suggest that B cells can regulate a human DTH reaction induced by Mtb.