Role of the polymeric Ig receptor in mucosal B cell homeostasis.
Secretory IgA (SIgA) is the most characteristic component of the mucosal immune system and has long been considered the major protective factor that prevents pathogens from invading hosts through the mucosae. Recent studies, however, have suggested that complete immunity against a range of mucosal bacterial and viral pathogens can be achieved in the absence of IgA. Therefore, to further dissect the role of SIgA, we generated mice deficient in the polymeric Ig receptor (pIgR(-/-) mice). As a result of an inability to transport dimeric IgA to the secretions, pIgR(-/-) mice are deficient in SIgA and accumulate circulating dimeric IgA, with serum levels 100-fold greater than those observed in normal mice. Examination of lamina propria mononuclear cells showed that pIgR(-/-) mice had approximately 3 times as many IgA-secreting cells as C57BL/6 mice. Further analysis showed that these cells displayed the differentiated IgA(+) B220(-) phenotype and accounted for a 2-fold increase in the number of lamina propria blast cells in the pIgR(-/-) mice. Subsequent experiments showed that OVA-specific CD4(+) T cell expansion following OVA feeding was not elevated in pIgR(-/-) mice. Furthermore, no differences in CD8(+) T cell tolerance or induction of influenza virus-specific CD8(+) T cells were detected in pIgR(-/-) mice compared with controls. Therefore, while SIgA is clearly involved in maintaining some parameters of mucosal homeostasis in the intestine, the mechanisms associated with its barrier function and the clinical consequences of its deficiency are yet to be identified.
Uren
Tania K
TK
Department of Microbiology and Immunology and Cooperative Research Center for Vaccine Technology, University of Melbourne, Parkville, Australia.
Johansen
Finn-Eirik
FE
Wijburg
Odilia L C
OL
Koentgen
Frank
F
Brandtzaeg
Per
P
Strugnell
Richard A
RA
D000284:Administration, Oral; D000818:Animals; D000921:Antibody-Producing Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D016175:B-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D019281:Dimerization; D018984:Epitopes, T-Lymphocyte / Q000008:administration & dosage / Q000276:immunology; D006706:Homeostasis / Q000235:genetics / Q000276:immunology*; D017098:IgA Deficiency / Q000235:genetics / Q000276:immunology; D007070:Immunoglobulin A / Q000096:biosynthesis / Q000097:blood; D007071:Immunoglobulin A, Secretory / Q000235:genetics; D007413:Intestinal Mucosa / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000235:genetics; D018655:Lymphocyte Count; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009061:Mouth Mucosa / Q000276:immunology / Q000378:metabolism; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D019056:Receptors, Polymeric Immunoglobulin / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D015854:Up-Regulation / Q000235:genetics / Q000276:immunology
D018984:Epitopes, T-Lymphocyte; D007070:Immunoglobulin A; D007071:Immunoglobulin A, Secretory; D019056:Receptors, Polymeric Immunoglobulin; D010047:Ovalbumin