Allergy & Asthma Symposium: Bridging Innate and Adaptive Immunity location:Bruges, Belgium date:28-29 May 2009
To investigate the underlying mechanisms of an established model of chemical-induced asthma, we transferred B- lymphocytes from sensitized mice to naïve mice.
BALB/c mice where dermally sensitized with 0.3% TDI (20 µl/ear), on day 1 and 8. On day 15, mice were sacrificed and the auricular lymph nodes isolated. B-lymphocytes (CD19+) where separated from the whole cell suspension and 175,000 cells where injected in the tail vein of naïve mice. Three days later, these mice received a single oropharyngeal challenge with 0.01% TDI (20 µl) or vehicle (acetone/olive oil) (controls). Airway reactivity to methacholine (resistance assessed by forced oscillation method, FlexiVent) and total and differential cell counts in the broncho-alveolar lavage (BAL) fluid were measured 24 hours after challenge.
Mice that received B-lymphocytes from TDI-sensitized mice showed a 3-fold increase in methacholine reactivity and an 8-fold increase in BAL neutrophils after challenge with TDI, compared to those challenged with vehicle. Transfer of the whole cell suspension without CD19+ lymphocytes (325,000 cells) resulted in a less pronounced airway reactivity to methacholine (1.5-fold) and a lower influx of neutrophils (1.3-fold) in the lungs.
We were able to passively sensitize naïve mice with B-lymphocytes from TDI-sensitized mice. Following passive sensitization and an airway challenge with TDI, these mice showed an “asthmatic” response. These data suggest a role for B-lymphocytes beside the already known important role of T-helper lymphocytes in chemical-induced asthma. We will confirm these results by using B-lymphocyte knock-out mice, transfer of CD19+ lymphocytes in SCID mice and depletion of the B-lymphocytes.