title: B Lymphocytes Are Required during the Early Priming of CD4+ T Cells for Clearance of Pneumocystis Infection in Mice.
abstract: B cells play a critical role in the clearance of Pneumocystis. In addition to production of Pneumocystis-specific Abs, B cells are required during the priming phase for CD4(+) T cells to expand normally and generate memory. Clearance of Pneumocystis was found to be dependent on Ag specific B cells and on the ability of B cells to secrete Pneumocystis-specific Ab, as mice with B cells defective in these functions or with a restricted BCR were unable to control Pneumocystis infection. Because Pneumocystis-specific antiserum was only able to partially protect B cell-deficient mice from infection, we hypothesized that optimal T cell priming requires fully functional B cells. Using adoptive transfer and B cell depletion strategies, we determined that optimal priming of CD4(+) T cells requires B cells during the first 2-3 d of infection and that this was independent of the production of Ab. T cells that were removed from Pneumocystis-infected mice during the priming phase were fully functional and able to clear Pneumocystis infection upon adoptive transfer into Rag1(-/-) hosts, but this effect was ablated in mice that lacked fully functional B cells. Our results indicate that T cell priming requires a complete environment of Ag presentation and activation signals to become fully functional in this model of Pneumocystis infection.
authors.affiliation: Division of Infectious Diseases, Department of Microbiology, Immunology, and Molecular Genetics, University of Kentucky College of Medicine, Lexington, KY 40536;
authors.forename: Michael M
authors.initials: MM
authors.lastname: Opata
authors.affiliation: Division of Infectious Diseases, Department of Microbiology, Immunology, and Molecular Genetics, University of Kentucky College of Medicine, Lexington, KY 40536;
authors.forename: Melissa L
authors.initials: ML
authors.lastname: Hollifield
authors.affiliation: Department of Microbiology, The University of Alabama at Birmingham, Birmingham, AL 35294;
authors.forename: Frances E
authors.initials: FE
authors.lastname: Lund
authors.affiliation: Department of Medicine, The University of Alabama at Birmingham, Birmingham, AL 35294;
authors.forename: Troy D
authors.initials: TD
authors.lastname: Randall
authors.affiliation: Genomics Institute of the Novartis Research Foundation, San Diego, CA 92121; and.
authors.forename: Robert
authors.initials: R
authors.lastname: Dunn
authors.affiliation: Division of Infectious Diseases, Department of Microbiology, Immunology, and Molecular Genetics, University of Kentucky College of Medicine, Lexington, KY 40536; bgarv0@email.uky.edu.
authors.forename: Beth A
authors.initials: BA
authors.lastname: Garvy
authors.affiliation: Department of Pharmacy Practice and Science, University of Kentucky College of Pharmacy, Lexington, KY 40536.
authors.forename: David J
authors.initials: DJ
authors.lastname: Feola
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D000908:Antibodies, Fungal / Q000096:biosynthesis*; D001402:B-Lymphocytes / Q000276:immunology* / Q000382:microbiology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000382:microbiology / Q000637:transplantation; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000382:microbiology; D049109:Cell Proliferation; D017353:Gene Deletion; D015870:Gene Expression; D018398:Homeodomain Proteins / Q000235:genetics / Q000276:immunology; D056724:Immunity, Humoral; D007156:Immunologic Memory; D008213:Lymphocyte Activation; D008212:Lymphocyte Depletion; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011010:Pneumocystis / Q000276:immunology*; D011020:Pneumonia, Pneumocystis / Q000276:immunology* / Q000382:microbiology / Q000473:pathology / Q000628:therapy
chemical_list: D000908:Antibodies, Fungal; D018398:Homeodomain Proteins; C064658:RAG-1 protein