Functional consequences of FcepsilonRIalpha up-regulation by IgE in human basophils.
These studies examine the functional changes that occur after up-regulation of FcepsilonRIalpha by immunoglobulin E (IgE) for human basophils. Basophils were cultured with and without IgE antibody (PS myeloma IgE or anti-gp120-specific IgE) for 1 week and challenged with anti-IgE, anti-FcepsilonRIalpha, or antigen for histamine and IL-4 secretion. There were no statistically significant changes in their response to anti-IgE or anti-receptor antibodies, as compared with controls incubated for the same period, whereas receptor expression increased an average of 4-fold. There was increased responsiveness to antigenic challenge, most notably at suboptimal concentrations of antigen (gp120 peptide-ovalbumin conjugate). For a 6-fold difference in cell surface density of gp120-specific IgE, there was a 2.2-fold change in antigen potency or 3-fold increases in histamine release at lower antigen concentrations. Similar results were found for secretion of IL-4. Basophil sensitivity, which is a measure of the density of antigen-specific IgE required for 50% of maximal secretion, was used to determine whether up-regulation of FcepsilonRIalpha was coordinated with up-regulation of other components of the IgE-signaling pathway. The results indicated up-regulation of FcepsilonRI is not always accompanied by changes that allow sensitivity to be maintained. These results indicate that functional up-regulation does occur but that its magnitude may be modulated because not all components of the signaling pathway are up-regulated in a balanced manner.
MacGlashan
D
D
Johns Hopkins Asthma and Allergy Center, Baltimore, Maryland 21224, USA. dmacglas@welch.jhu.edu
Schroeder
J T
JT
D000888:Antibodies, Anti-Idiotypic / Q000494:pharmacology; D001491:Basophils / Q000276:immunology / Q000378:metabolism*; D002478:Cells, Cultured; D004306:Dose-Response Relationship, Immunologic; D005434:Flow Cytometry; D006801:Humans; D007073:Immunoglobulin E / Q000494:pharmacology*; D018793:Interleukin-13 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D017455:Receptors, IgE / Q000096:biosynthesis* / Q000235:genetics; D015854:Up-Regulation / Q000187:drug effects*
D000888:Antibodies, Anti-Idiotypic; D018793:Interleukin-13; D017455:Receptors, IgE; C026408:anti-IgE antibodies; D015847:Interleukin-4; D007073:Immunoglobulin E