title: Airway hyper-reactivity mediated by B-1 cell immunoglobulin M antibody generating complement C5a at 1 day post-immunization in a murine hapten model of non-atopic asthma.
abstract: Contact skin immunization of mice with reactive hapten antigen and subsequent airway challenge with the same hapten induces immediate airflow obstruction and subsequent airway hyper-reactivity (AHR) to methacholine challenge, which is dependent on B cells but not on T cells. This responsiveness to airway challenge with antigen is elicited as early as 1 day postimmunization and can be adoptively transferred to naïve recipients via 1-day immune cells. Responses are absent in 1-day immune B-cell-deficient JH(-/-) mice and B-1 B-cell-deficient xid male mice, as well as in recipients of 1-day immune cells depleted of cells with the B-1 cell phenotype (CD19(+) B220(+) CD5(+)). As B-1 cells produce immunoglobulin M (IgM), we sought and found significantly increased numbers of anti-hapten IgM-producing cells in the spleen and lymph nodes of 1-day immune wild-type mice, but not in xid mice. Then, we passively immunized naive mice with anti-hapten IgM monoclonal antibody and, following airway hapten challenge of the recipients, we showed both immediate airflow obstruction and AHR. In addition, AHR was absent in complement C5 and C5a receptor-deficient mice. In summary, this study of the very early elicited phase of a hapten asthma model suggests, for the first time, a role of B-1 cells in producing IgM to activate complement to rapidly mediate asthma airway reactivity only 1 day after immunization.
authors.affiliation: Section of Allergy and Clinical Immunology, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT, USA. ivana.kawikova@yale.edu
authors.forename: Ivana
authors.initials: I
authors.lastname: Kawikova
authors.forename: Vipin
authors.initials: V
authors.lastname: Paliwal
authors.forename: Marian
authors.initials: M
authors.lastname: Szczepanik
authors.forename: Atsuko
authors.initials: A
authors.lastname: Itakura
authors.forename: Mieko
authors.initials: M
authors.lastname: Fukui
authors.forename: Regis A
authors.initials: RA
authors.lastname: Campos
authors.forename: Gregory P
authors.initials: GP
authors.lastname: Geba
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Homer
authors.forename: Bettina P
authors.initials: BP
authors.lastname: Iliopoulou
authors.forename: Jordan S
authors.initials: JS
authors.lastname: Pober
authors.forename: Ryohei F
authors.initials: RF
authors.lastname: Tsuji
authors.forename: Philip W
authors.initials: PW
authors.lastname: Askenase
mesh_terms: D000818:Animals; D001249:Asthma / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D001402:B-Lymphocytes / Q000276:immunology*; D016535:Bronchial Hyperreactivity / Q000276:immunology* / Q000473:pathology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D015936:Complement C5a / Q000276:immunology*; D004195:Disease Models, Animal; D005260:Female; D006241:Haptens / Q000276:immunology; D007114:Immunization / Q000379:methods; D007075:Immunoglobulin M / Q000276:immunology*; D008168:Lung / Q000473:pathology; D008297:Male; D016210:Methacholine Chloride / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D012129:Respiratory Function Tests; D012137:Respiratory System
chemical_list: D006241:Haptens; D007075:Immunoglobulin M; D016210:Methacholine Chloride; D015936:Complement C5a