Mucosal B cell deficiency in IgA-/- mice abrogates the development of allergic lung inflammation.
We have investigated the consequence of lack of IgA on host immunity using a murine model of allergic lung inflammation. Mice with a targeted disruption of the alpha-switch region and 5' H chain gene (IgA(-/-) mice), which lack total IgA, developed significantly reduced pulmonary inflammation with fewer inflammatory cells in lung tissue and bronchoalveolar lavage fluids, as well as reduced levels of total and IgG1 OVA-specific Abs and decreased IL-4 and IL-5 in bronchoalveolar lavage fluids compared with IgA(+/+) controls, following allergen sensitization and challenge. This defect was attributable to fewer B cells in the lungs of IgA(-/-) mice. Polymeric IgR-deficient (pIgR(-/-)) mice, which lack the receptor that transports polymeric IgA across the mucosal epithelium where it is cleaved to form secretory IgA, were used to assess the contribution of secretory IgA vs total IgA in the induction of allergic lung inflammation. pIgR(-/-) and pIgR(+/+) mice had comparable levels of inflammation, demonstrating that IgA bound to secretory component is not necessary for the development of allergic lung inflammation, although this does not necessarily rule out a role for transudated IgA in lung secretions because of "mucosal leakiness" in these mice. The results indicate that Ag-specific B cells are required at mucosal surfaces for induction of inflammation and likely function as major APCs in the lung for soluble protein Ags.
Center for Immunology and Microbial Disease, Albany Medical College, 47 New Scotland Avenue, Albany, NY 12208, USA.
Paul M
PM
Arnaboldi
Melissa J
MJ
Behr
Dennis W
DW
Metzger
D000281:Administration, Intranasal; D000485:Allergens / Q000008:administration & dosage / Q000276:immunology; D000818:Animals; D016175:B-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D002464:Cell Migration Inhibition; D017098:IgA Deficiency / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D007070:Immunoglobulin A / Q000378:metabolism; D007249:Inflammation / Q000276:immunology / Q000473:pathology / Q000517:prevention & control; D008168:Lung / Q000276:immunology / Q000473:pathology*; D008231:Lymphopenia / Q000235:genetics / Q000276:immunology* / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D012130:Respiratory Hypersensitivity / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D020545:Respiratory Mucosa / Q000276:immunology* / Q000473:pathology*
D000485:Allergens; D007070:Immunoglobulin A; D010047:Ovalbumin