MICE DEFICIENT FOR THE IL-3 GM-CSF/IL-5 BETA-C RECEPTOR EXHIBIT LUNG PATHOLOGY AND IMPAIRED IMMUNE-RESPONSE, WHILE BETA-IL3 RECEPTOR-DEFICIENT MICE ARE NORMAL/

The receptors for IL-3, GM-CSF, and IL-5 share a common beta subunit ( beta c), and mice have an additional IL-3 beta subunit (beta(IL3)) We have independently generated mice carrying null mutations of each mole cule, beta c mutant bone marrow showed no response to GM-CSF or IL-5, whereas IL-3 stimulation of beta c or beta(IL3) mutant bone marrow was normal. beta c mutant mice showed lung pathology consisting of lympho cytic infiltration and areas resembling alveolar proteinosis, and also exhibited low basal numbers of eosinophils. Infection of beta c mutan t mice by Nippostrongylus brasiliensis resulted in the absence of bloo d and lung eosinophilia. Animals repopulated with beta c mutant bone m arrow cells showed slower leukocyte recovery and reduced eosinophil nu mbers, These data define the role of beta c in vivo, and show a phenot ype that is likely to be the cumulative effect of loss of GM-CSF and I L-5 stimulation.