title: Differential and site specific impact of B cells in the protective immune response to Mycobacterium tuberculosis in the mouse.
abstract: Cell-mediated immune responses are known to be critical for control of mycobacterial infections whereas the role of B cells and humoral immunity is unclear. B cells can modulate immune responses by secretion of immunoglobulin, production of cytokines and antigen-presentation. To define the impact of B cells in the absence of secreted immunoglobulin, we analyzed the progression of Mycobacterium tuberculosis (Mtb) infection in mice that have B cells but which lack secretory immunoglobulin (AID(-/-)µS(-/-)mice). AID(-/-)µS(-/-) mice accumulated a population of activated B cells in the lungs when infected and were more susceptible to aerosol Mtb when compared to wild type (C57BL/6) mice or indeed mice that totally lack B cells. The enhanced susceptibility of AID(-/-)µS(-/-) mice was not associated with defective T cell activation or expression of a type 1 immune response. While delivery of normal serum to AID(-/-)µS(-/-) mice did not reverse susceptibility, susceptibility in the spleen was dependent upon the presence of B cells and susceptibility in the lungs of AID(-/-)µS(-/-)mice was associated with elevated expression of the cytokines IL-6, GM-CSF, IL-10 and molecules made by alternatively activated macrophages. Blocking of IL-10 signaling resulted in reversal of susceptibility in the spleens and lungs of AID(-/-)µS(-/-) mice. These data support the hypothesis that B cells can modulate immunity to Mtb in an organ specific manner via the modulation of cytokine production and macrophage activation.
authors.affiliation: Trudeau Institute Inc., Saranac Lake, New York, United States of America.
authors.forename: Egídio
authors.initials: E
authors.lastname: Torrado
authors.forename: Jeffrey J
authors.initials: JJ
authors.lastname: Fountain
authors.forename: Richard T
authors.initials: RT
authors.lastname: Robinson
authors.forename: Cynthia A
authors.initials: CA
authors.lastname: Martino
authors.forename: John E
authors.initials: JE
authors.lastname: Pearl
authors.forename: Javier
authors.initials: J
authors.lastname: Rangel-Moreno
authors.forename: Michael
authors.initials: M
authors.lastname: Tighe
authors.forename: Robert
authors.initials: R
authors.lastname: Dunn
authors.forename: Andrea M
authors.initials: AM
authors.lastname: Cooper
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D051379:Mice; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D014376:Tuberculosis / Q000276:immunology*
chemical_list: D015850:Interleukin-6; D016753:Interleukin-10; D016178:Granulocyte-Macrophage Colony-Stimulating Factor