Analysis of Tcrvb8, Il4, and Ifg as genetic predisposition factors for atopic IgE response in a murine model.
Allergen-induced synthesis of lgE Abs in genetically predisposed individuals constitutes the hallmark of allergic diseases; however, the molecular basis of this genetic predisposition remains unknown. T cell cytokines lL-4 and IFN-gamma reciprocally regulate lgE synthesis and are potential genetic factors governing atopy. To examine the inheritance patterns of IgE responsiveness and address the role of these cytokines as genetic predisposition factors, in this study we established a MHC-identical mouse colony comprising crosses between two inbred strains of mouse, A.SW and SJL, respectively representing high and low IgE responder phenotypes. Segregation analysis with 149 [(A.SW x SJL)F1 x SJL] backcross and 148 [(A.SW x SJL)F1 x F1]F2 mice suggested that persistent high IgE responsiveness was inherited as a simple Mendelian dominant trait under the control of a single non-MHC, autosomal gene of major effect in these strains. Since SJL lacked Tcrvb8 genes, we examined the possibility of Tcrvb8 as a candidate gene for IgE responsiveness. The results suggested association of neither the Tcrvb8 gene nor its expression with allergen-induced IgE phenotype. Furthermore, microsatellite marker and gene sequencing analyses revealed that neither of the ll4 and lfg genes was associated with IgE phenotype. Moreover, correlation studies between IgE and cytokine levels in splenocyte cultures indicated that IgE levels were moderately to poorly correlated with IL-4 and IFN-gamma levels. It is concluded that even though expression of Tcrvb8, II4, and Ifg genes may play pivotal roles in IgE regulation, these genes per se do not contribute to genetic predisposition of allergen-induced IgE hyperresponsiveness in these strains of mice.
Venugopal
G
G
Department of Immunology, University of Manitoba, Winnipeg, Canada.
Yang
M
M
Luo
Z
Z
Salo
D
D
Cheang
M
M
Mohapatra
S S
SS
D000818:Animals; D001483:Base Sequence; D005260:Female; D006969:Hypersensitivity, Immediate / Q000235:genetics* / Q000276:immunology; D007073:Immunoglobulin E / Q000097:blood / Q000276:immunology*; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology*; D015847:Interleukin-4 / Q000235:genetics / Q000276:immunology*; D008297:Male; D051379:Mice; D008805:Mice, Inbred A; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000276:immunology*
D016693:Receptors, Antigen, T-Cell, alpha-beta; D015847:Interleukin-4; D007073:Immunoglobulin E; D007371:Interferon-gamma