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The Journal of Immunology, 1999, 163: 3064-3070.
Copyright © 1999 by The American Association of Immunologists

Migration of Antigen-Presenting B Cells from Peripheral to Mucosal Lymphoid Tissues May Induce Intestinal Antigen-Specific IgA Following Parenteral Immunization1

Susan E. Coffin2,*,{dagger}, Stephanie L. Clark*, Nico A. Bos{ddagger}, Jeffery O. Brubaker* and Paul A. Offit*,{dagger}

* Division of Immunologic and Infectious Diseases, Children’s Hospital of Philadelphia, Philadelphia, PA 19104; {dagger} University of Pennsylvania School of Medicine, Philadelphia, PA 19104; {ddagger} University of Groningen, Groningen, The Netherlands; and § Wistar Institute of Anatomy and Biology, Philadelphia, PA 19104

Parenterally administered immunizations have long been used to induce protection from mucosal pathogens such as Bordetella pertussis and influenza virus. We previously found that i.m. inoculation of mice with the intestinal pathogen, rotavirus, induced virus-specific Ab production by intestinal lymphocytes. We have now used adoptive transfer studies to identify the cell types responsible for the generation of virus-specific Ab production by gut-associated lymphoid tissue (GALT) after i.m. immunization. Three days after i.m. immunization with rotavirus, cells obtained from the draining peripheral lymph nodes of donor mice were transferred into naive recipient mice. We found that intestinal lymphocytes produced rotavirus-specific Igs (IgM, IgA, and IgG) 2 wk after transfer of either unfractionated cells, or unfractionated cells rendered incapable of cellular division by mitomycin C treatment. Additional studies demonstrated that rotavirus-specific IgA, but not IgG, was produced by intestinal lymphocytes after transfer of purified B cells. Ig allotype analysis revealed that rotavirus-specific IgA was produced by intestinal B cells of recipient origin, suggesting that migration of Ag-presenting B cells from peripheral lymphoid tissues to GALT may contribute to the generation of mucosal IgA responses after parenteral immunization. Strategies that promote Ag uptake and presentation by B cells may enhance mucosal IgA production following parenteral immunization.




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