The Role of B Cells in the Immune Response to Mycobacterium tuberculosis. (43.3)

Abstract

Abstract The role of humoral immunity in the immune response to Mycobacterium tuberculosis (Mtb) is poorly defined. B cells form aggregates with features of germinal centers and are prominent components of the lung granuloma in Mtb-infected humans, mice and macaques. Using muMT B cell-deficient mice, we showed that B cells were required for optimal granulomatous response and protection upon aerosol infection. muMT mice were more susceptible to Mtb with increased mortality and elevated lung bacterial burden. B cell-deficiency also resulted in exacerbated immunopathology with increased neutrophil influx and IL-10 production independent of tissue bacterial load. Transfer of B cells reversed the phenotypes of the muMT mice. This occurred in the presence of immunoglobulins (Igs) in the serum but without the presence of lung B cells. We showed that engagement of distinct Fcγ receptors (FcγR) divergently affected susceptibility to Mtb. Mice lacking activating FcγR showed increased mortality and bacterial load with enhanced lung neutrophil influx and IL-10 expression compared to wildtype, whereas mice lacking inhibitory FcγRIIB exhibited an augmented lung Th1 response. Thus, B cells via their ability to produce Igs may regulate T cell responses by immune complex engagement of FcγR on antigen presenting cells. The mechanisms by which B cells modulate the immune response to Mtb are being characterized by testing the immune response of transgenic mice deficient in B cells or Igs to infection.