In vivo murine CD23 destabilization enhances CD23 shedding and IgE synthesis.
To investigate the effects of in vivo CD23 destabilization on CD23 shedding and IgE production, an anti-CD23 stalk monoclonal (19G5), previously shown to enhance proteolysis of CD23 in vitro, was utilized. Compared to isotype control-treated mice, BALB/cJ mice injected with 19G5 displayed significantly enhanced serum soluble CD23 and IgE. Soluble CD23 and IgE levels were also increased in 19G5-treated C57BL/6J mice (intermediate IgE responders); however, the kinetics of the responses differed between the high (BALB/cJ) and intermediate responder mice, suggesting a potential role for CD23 in regulating IgE responder status. The 19G5-induced IgE response was dependent on IL-4 and independent of CD21 as demonstrated through use of IL-4Ralpha and CD21/35-deficient mice, respectively. Overall, the data provide a direct demonstration for CD23's role in regulating IgE production in vivo and suggest that therapies aimed at stabilizing cell surface CD23 would be beneficial in controlling allergic disease.
Ford
Jill W
JW
Department of Microbiology and Immunology, Virginia Commonwealth University, PO Box 980678, Richmond, VA 23298, USA. fordjw@vcu.edu
Kilmon
Michelle A
MA
Haas
Karen M
KM
Shelburne
Anne E
AE
Chan-Li
Yee
Y
Conrad
Daniel H
DH
D000534:Alum Compounds / Q000737:chemistry; D000818:Animals; D000947:Antigens, Helminth / Q000276:immunology; D002462:Cell Membrane / Q000378:metabolism; D007114:Immunization; D007073:Immunoglobulin E / Q000096:biosynthesis* / Q000097:blood; D007074:Immunoglobulin G / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D009559:Nippostrongylus / Q000276:immunology*; D017464:Receptors, Complement 3d; D017455:Receptors, IgE / Q000097:blood*; D015398:Signal Transduction; D012834:Silver / Q000378:metabolism; D017206:Strongylida Infections / Q000276:immunology*
D000534:Alum Compounds; D000947:Antigens, Helminth; D007074:Immunoglobulin G; D017464:Receptors, Complement 3d; D017455:Receptors, IgE; D015847:Interleukin-4; C041524:aluminum sulfate; D007073:Immunoglobulin E; D012834:Silver