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) (20µl/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 (20µl) 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.
Highlights
Many studies have demonstrated a crucial role for Tlymphocytes and the cytokines they produce in the development of allergic asthma [1]
The main findings of this study were that B-lymphocytes play an important role in the induction of Airway hyperreactivity (AHR) and airway inflammation, even without the presence of T-lymphocytes
Studies on B-lymphocytes and their role in the immune response and in asthma have almost exclusively focused on their implication in the humoral response, i.e. the production of antigen-specific immunoglobulins E (IgE) antibodies
Summary
Many studies have demonstrated a crucial role for Tlymphocytes and the cytokines they produce in the development of allergic asthma [1]. Not all asthma is allergic (or atopic) asthma, and in a substantial proportion of asthmatics there seems to be little or no implication of specific IgE in the pathogenesis of the disease [4] This is most notably the case in immunologically mediated occupational asthma (OA) caused by some sensitizing chemicals, such as diisocyanates [5]. Diisocyanates are low molecular weight chemicals widely used in industry for the production of e.g. polyurethane foams, vanish, paint, and isolation material [6,7]. They are an important cause of occupational asthma [5]. Lavaud et al showed that showed that treatment of patients with severe occupational asthma due to low molecular weight agents, with the anti-IgE antibody omalizumab lowered the levels of total serum IgE and in most cases improved FEV1, but did not result in complete controlled asthma [9]
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