title: Expression of activation-induced cytidine deaminase enhances the clearance of pneumococcal pneumonia: evidence of a subpopulation of protective anti-pneumococcal B1a cells.
abstract: We describe a protective early acquired immune response to pneumococcal pneumonia that is mediated by a subset of B1a cells. Mice deficient in B1 cells (xid), or activation-induced cytidine deaminase (AID(-/-) ), or invariant natural killer T (iNKT) cells (Jα18(-/-) ), or interleukin-13 (IL-13(-/-) ) had impaired early clearance of pneumococci in the lung, compared with wild-type mice. In contrast, AID(-/-) mice adoptively transferred with AID(+/+) B1a cells, significantly cleared bacteria from the lungs as early as 3 days post infection. We show that this early bacterial clearance corresponds to an allergic contact sensitivity-like cutaneous response, probably due to a subpopulation of initiating B1a cells. In the pneumonia model, these B1a cells were found to secrete higher affinity antigen-specific IgM. In addition, as in contact sensitivity, iNKT cells were required for the anti-pneumococcal B1a cell initiating response, probably through early production of IL-13, given that IL-13(-/-) mice also failed to clear infection. Our study is the first to demonstrate the importance of AID in generating an appropriate B1a cell response to pathogenic bacteria. Given the antibody affinity and pneumonia resistance data, natural IgM produced by conventional B1a cells are not responsible for pneumonia clearance compared with the AID-dependent subset.
authors.affiliation: Section of Allergy and Clinical Immunology, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT, USA.|Department of Infection Control, Fukushima Medical University, Hikarigaoka, Japan.
authors.forename: Natsuo
authors.initials: N
authors.lastname: Yamamoto
authors.affiliation: Section of Allergy and Clinical Immunology, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: Steven M
authors.initials: SM
authors.lastname: Kerfoot
authors.affiliation: Section of Allergy and Clinical Immunology, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: Andrew T
authors.initials: AT
authors.lastname: Hutchinson
authors.affiliation: Section of Allergy and Clinical Immunology, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: Charles S
authors.initials: CS
authors.lastname: Dela Cruz
authors.affiliation: Department of Infection Control, Fukushima Medical University, Hikarigaoka, Japan.
authors.forename: Naomi
authors.initials: N
authors.lastname: Nakazawa
authors.affiliation: Section of Allergy and Clinical Immunology, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT, USA.|Department of Medical Biology, Jagiellonian University Medical College, Krakow, Poland.
authors.forename: Marian
authors.initials: M
authors.lastname: Szczepanik
authors.affiliation: Section of Allergy and Clinical Immunology, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT, USA.|Department of Medical Biology, Jagiellonian University Medical College, Krakow, Poland.
authors.forename: Monika
authors.initials: M
authors.lastname: Majewska-Szczepanik
authors.affiliation: Section of Allergy and Clinical Immunology, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT, USA.|Department of Immunology, Jagiellonian University Medical College, Krakow, Poland.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Nazimek
authors.affiliation: Department of Infection Control, Fukushima Medical University, Hikarigaoka, Japan.
authors.forename: Noboru
authors.initials: N
authors.lastname: Ohana
authors.affiliation: Section of Allergy and Clinical Immunology, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT, USA.|Department of Immunology, Jagiellonian University Medical College, Krakow, Poland.
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Bryniarski
authors.affiliation: Department of Infection Control, Fukushima Medical University, Hikarigaoka, Japan.
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Mori
authors.affiliation: Department of Molecular Genetics, Graduate School of Medical Science, Kanazawa University, Kanazawa, Japan.
authors.forename: Masamichi
authors.initials: M
authors.lastname: Muramatsu
authors.affiliation: Department of Infection Control, Fukushima Medical University, Hikarigaoka, Japan.
authors.forename: Keiji
authors.initials: K
authors.lastname: Kanemitsu
authors.affiliation: Section of Allergy and Clinical Immunology, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: Philip W
authors.initials: PW
authors.lastname: Askenase
mesh_terms: D056704:Adaptive Immunity; D019264:Adoptive Transfer; D000077329:Agammaglobulinaemia Tyrosine Kinase; D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology; D001402:B-Lymphocytes / Q000201:enzymology* / Q000276:immunology / Q000382:microbiology / Q000637:transplantation; D003167:Complement Activation; D003564:Cytidine Deaminase / Q000172:deficiency / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D003877:Dermatitis, Contact / Q000201:enzymology / Q000276:immunology / Q000382:microbiology; D004195:Disease Models, Animal; D005838:Genotype; D007075:Immunoglobulin M / Q000276:immunology / Q000378:metabolism; D018793:Interleukin-13 / Q000172:deficiency / Q000235:genetics; D008168:Lung / Q000201:enzymology* / Q000276:immunology / Q000382:microbiology; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D018345:Mice, Knockout; D055611:Natural Killer T-Cells / Q000276:immunology / Q000382:microbiology; D010587:Phagocytosis; D010641:Phenotype; D011018:Pneumonia, Pneumococcal / Q000201:enzymology* / Q000276:immunology / Q000382:microbiology; D011505:Protein-Tyrosine Kinases / Q000276:immunology / Q000378:metabolism; D013154:Spleen / Q000201:enzymology / Q000276:immunology / Q000382:microbiology; D013296:Streptococcus pneumoniae / Q000276:immunology* / Q000472:pathogenicity; D013997:Time Factors; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
chemical_list: D000942:Antigens, Bacterial; D016207:Cytokines; D007075:Immunoglobulin M; D018793:Interleukin-13; D011505:Protein-Tyrosine Kinases; D000077329:Agammaglobulinaemia Tyrosine Kinase; C000625951:Btk protein, mouse; D000098830:AICDA (Activation-Induced Cytidine Deaminase); D003564:Cytidine Deaminase
keywords: B1a cells; IgM antibody; activation-induced cytidine deaminase; interleukin-13; invariant natural killer T cells; pneumococcal pneumonia