IL-4-Responsive B Cells Are Detrimental During Chronic Tuberculosis Infection in Mice.

In tuberculosis, T cell-mediated immunity is extensively studied whilst B cells received limited attention in human and mice. Of interest, () does increase IL-4 Receptor-alpha (IL4Rα) expression in murine B cells. To better understand the role of IL4Rα signalling in B cells, we compared wild type mice with B cell-specific IL4Rα deficient mice (mb1IL-4Rα mice). Chronic aerosol infection in mb1IL-4Rα mice reduced lung and spleen bacterial burdens, compared to littermate (IL-4Rα) control animals. Consequently, lung pathology, inflammation and inducible nitric oxide synthase (iNOS) expression were reduced in the lungs of mb1IL-4Rα mice, which was also accompanied by increased lung IgA and decreased IgG1 levels. Furthermore, intratracheal adoptive transfer of wild-type B cells into B cell-specific IL4Rα deficient mice reversed the protective phenotype. Moreover, constitutively mCherry expressing showed decreased association with B cells from mb1IL-4Rα mice . In addition, supernatants from -exposed B cells of mb1IL-4Rα mice also increased the ability of macrophages to produce nitric oxide, IL-1β, IL-6 and TNF. Together, this demonstrates that IL-4-responsive B cells are detrimental during the chronic phase of tuberculosis in mice with perturbed antibody profiles, inflammatory cytokines and and levels in the lungs.