title: B-lymphocytes as key players in chemical-induced asthma.
abstract: T-lymphocytes and B-lymphocytes are key players in allergic asthma, with B-lymphocytes producing antigen-specific immunoglobulins E (IgE). We used a mouse model of chemical-induced asthma and transferred B-lymphocytes from sensitized animals into naïve wild type mice, B-lymphocyte knock-out (B-KO) mice or severe combined immunodeficiency (SCID) mice. On days 1 and 8, BALB/c mice were dermally sensitized with 0.3% toluene diisocyanate (TDI) (20 µl/ear). On day 15, mice were euthanized and the auricular lymph nodes isolated. B-lymphocytes (CD19(+)) were separated from the whole cell suspension and 175,000 cells were injected in the tail vein of naïve wild type, B-KO or SCID mice. Three days later, the mice received a single oropharyngeal challenge with 0.01% TDI (20 µl) or vehicle (acetone/olive oil (AOO)) (controls). Airway reactivity to methacholine and total and differential cell counts in the bronchoalveolar lavage (BAL) fluid were measured 24 hours after challenge. B-lymphocytes of AOO or TDI-sensitized mice were characterized for the expression of surface markers and production of cytokines. We found that transfer of B-cells obtained from mice dermally sensitized to toluene diisocyanate (TDI) into naïve wild type mice, B-KO mice or SCID mice led, within three days, to an acute asthma-like phenotype after an airway challenge with TDI. This response was specific and independent of IgE. These B-lymphocytes showed antigen presenting capacities (CD80/CD86 and CD40) and consisted of B effector (Be)2- (IL-4) and Be1-lymphocytes (IFN-γ). The transferred B-lymphocytes were visualized near large airways, 24 hours after TDI challenge. Thus, B-lymphocytes can provoke an asthmatic response without the action of T-lymphocytes and without major involvement of IgE.
authors.affiliation: Laboratory for Occupational and Environmental Toxicology, Leuven, Belgium.
authors.forename: Vanessa
authors.initials: V
authors.lastname: De Vooght
authors.affiliation: Center for Molecular and Vascular Biology, Leuven, Belgium.
authors.forename: Vincent
authors.initials: V
authors.lastname: Carlier
authors.affiliation: Laboratory for Occupational and Environmental Toxicology, Leuven, Belgium.
authors.forename: Fien C
authors.initials: FC
authors.lastname: Devos
authors.affiliation: Laboratory for Occupational and Environmental Toxicology, Leuven, Belgium.
authors.forename: Steven
authors.initials: S
authors.lastname: Haenen
authors.affiliation: Translational Cell & Tissue Research, KU Leuven, Leuven, Belgium.
authors.forename: Erik
authors.initials: E
authors.lastname: Verbeken
authors.affiliation: Laboratory for Occupational and Environmental Toxicology, Leuven, Belgium.
authors.forename: Benoit
authors.initials: B
authors.lastname: Nemery
authors.affiliation: Laboratory for Occupational and Environmental Toxicology, Leuven, Belgium.
authors.forename: Peter H M
authors.initials: PH
authors.lastname: Hoet
authors.affiliation: Laboratory for Occupational and Environmental Toxicology, Leuven, Belgium.
authors.forename: Jeroen A J
authors.initials: JA
authors.lastname: Vanoirbeek
mesh_terms: D000818:Animals; D001249:Asthma / Q000139:chemically induced* / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D016175:B-Lymphocyte Subsets / Q000276:immunology* / Q000473:pathology; D018122:B7-1 Antigen / Q000235:genetics / Q000276:immunology; D051940:B7-2 Antigen / Q000235:genetics / Q000276:immunology; D016085:Bronchoconstrictor Agents / Q000494:pharmacology; D019013:CD40 Antigens / Q000235:genetics / Q000276:immunology; D004195:Disease Models, Animal; D007073:Immunoglobulin E / Q000235:genetics / Q000276:immunology; D008297:Male; D016210:Methacholine Chloride / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D016513:Mice, SCID; D014051:Toluene 2,4-Diisocyanate / Q000633:toxicity
chemical_list: D018122:B7-1 Antigen; D051940:B7-2 Antigen; D016085:Bronchoconstrictor Agents; D019013:CD40 Antigens; C497965:Cd86 protein, mouse; D016210:Methacholine Chloride; D014051:Toluene 2,4-Diisocyanate; D007073:Immunoglobulin E