title: B lymphocytes regulate airway granulocytic inflammation and cytokine production in a murine model of fungal allergic asthma.
abstract: Sensitization to fungi often leads to a severe form of asthma that is particularly difficult to manage clinically, resulting in increased morbidity and hospitalizations in these patients. Although B lymphocytes might exacerbate asthma symptoms through the production of IgE, these cells might also be important in the protective response against inhaled fungi. Through cytokine release and T-cell interactions, these lymphocytes might also influence the development and maintenance of airway wall fibrosis. J(H)(-/-) mice lack the JH gene for the heavy chain component of antibodies, which is critical for B-cell function and survival. These animals have facilitated the elucidation of the role of B lymphocytes in a number of immune responses; however, J(H)(-/-) mice have not been used to study fungal allergy. In this study, we examined the role of B lymphocytes using an Aspergillus fumigatus murine fungal aeroallergen model that mimics human airway disease that is triggered by environmental fungal exposure. We compared disease progression in sensitized wild-type BALB/c and J(H)(-/-) mice that were exposed to repeated fungal exposure and found no differences in airway hyperresponsiveness, overall pulmonary inflammation or collagen deposition around the large airways. However, the levels of the Th2-type cytokines IL-4 and IL-13 were significantly attenuated in the airways of J(H)(-/-) mice relative to the BALB/c controls. By contrast, levels of the inflammatory cytokines IL-17A and IL-6 were significantly elevated in the J(H)(-/-) animals, and there was significantly more robust airway eosinophilia and neutrophilia than in control animals. Taken together, these findings demonstrate that B lymphocytes help to regulate granulocytic responses to fungal exposure in the pulmonary compartment.
authors.forename: Sumit
authors.initials: S
authors.lastname: Ghosh
authors.forename: Scott A
authors.initials: SA
authors.lastname: Hoselton
authors.forename: Scott V
authors.initials: SV
authors.lastname: Asbach
authors.forename: Breanne N
authors.initials: BN
authors.lastname: Steffan
authors.forename: Steve B
authors.initials: SB
authors.lastname: Wanjara
authors.forename: Glenn P
authors.initials: GP
authors.lastname: Dorsam
authors.forename: Jane M
authors.initials: JM
authors.lastname: Schuh
mesh_terms: D000818:Animals; D001249:Asthma / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D001402:B-Lymphocytes / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D015153:Blotting, Western; D016535:Bronchial Hyperreactivity / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D001992:Bronchoalveolar Lavage Fluid; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D006098:Granulocytes / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D006801:Humans; D007073:Immunoglobulin E; D007143:Immunoglobulin Heavy Chains / Q000502:physiology; D007133:Immunoglobulin Joining Region / Q000502:physiology; D008168:Lung / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D011014:Pneumonia / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013172:Spores, Fungal / Q000472:pathogenicity
chemical_list: D016207:Cytokines; D007143:Immunoglobulin Heavy Chains; D007133:Immunoglobulin Joining Region; D012333:RNA, Messenger; D007073:Immunoglobulin E