title: B-cell function in canine X-linked severe combined immunodeficiency.
abstract: Canine X-linked severe combined immunodeficiency (XSCID) is due to mutations in the common gamma (gammac) subunit of the IL-2, IL-4, IL-7, IL-9 and IL-15 receptors and has a similar clinical phenotype to human XSCID. We have previously shown that the block in T-cell development is more profound in XSCID dogs than in genetically engineered gamma c-deficient mice. In this study we evaluated the B-cell function in XSCID dogs. In contrast to the marked decrease in peripheral B-cells in gamma c-deficient mice, XSCID dogs have increased proportions and numbers of peripheral B-cells as observed in XSCID boys. Canine XSCID B-cells do not proliferate following stimulation with the T-cell-dependent B-cell mitogen, pokeweed mitogen (PWM); however, they proliferate normally in response to the T-cell-independent B-cell mitogen, formalin-fixed, heat-killed Staphylococcus aureus. Canine XSCID B-cells are capable of producing IgM but are incapable of normal class-switching to IgG antibody production as demonstrated by in vitro stimulation with PWM and immunization with the T-cell-dependent antigen, bacteriophage PhiX174. Similar results have been reported for XSCID boys. Thus, it appears that gamma c-dependent cytokines have differing roles in human and canine B-cell development than in the mouse making the XSCID dog a valuable model for studying the role of these cytokines in B-cell development and function.
authors.affiliation: Department of Clinical Studies, School of Veterinary Medicine, University of Pennsylvania, 3850 Spruce St., Philadelphia, PA, USA.
authors.forename: B J
authors.initials: BJ
authors.lastname: Hartnett
authors.forename: R L
authors.initials: RL
authors.lastname: Somberg
authors.forename: S
authors.initials: S
authors.lastname: Krakowka
authors.forename: H D
authors.initials: HD
authors.lastname: Ochs
authors.forename: H
authors.initials: H
authors.lastname: HogenEsch
authors.forename: P F
authors.initials: PF
authors.lastname: Moore
authors.forename: K I
authors.initials: KI
authors.lastname: Weinberg
authors.forename: P J
authors.initials: PJ
authors.lastname: Felsburg
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000502:physiology*; D004283:Dog Diseases / Q000235:genetics / Q000276:immunology*; D004285:Dogs; D005434:Flow Cytometry / Q000662:veterinary; D008040:Genetic Linkage; D006801:Humans; D007136:Immunoglobulins / Q000096:biosynthesis; D051379:Mice; D010641:Phenotype; D016511:Severe Combined Immunodeficiency / Q000235:genetics / Q000276:immunology / Q000662:veterinary*; D013211:Staphylococcus aureus / Q000276:immunology; D014960:X Chromosome
chemical_list: D007136:Immunoglobulins