Differential and Site Specific Impact of B Cells in the Protective Immune Response to Mycobacterium tuberculosis in the Mouse |
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Authors: | Egídio Torrado Jeffrey J. Fountain Richard T. Robinson Cynthia A. Martino John E. Pearl Javier Rangel-Moreno Michael Tighe Robert Dunn Andrea M. Cooper |
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Affiliation: | 1. Trudeau Institute Inc., Saranac Lake, New York, United States of America.; 2. Division of Allergy, Immunology and Rheumatology, Department of Medicine, University of Rochester Medical Center, Rochester, New York, United States of America.; 3. Biogen Idec, Cambridge, Massachusetts, United States of America, and San Diego, California, United States of America.; Institut Pasteur, France, |
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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. |
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