title: Adrenergic regulation of IgE involves modulation of CD23 and ADAM10 expression on exosomes.
abstract: Soluble CD23 plays a role in the positive regulation of an IgE response. Engagement of the β2 adrenergic receptor (β2AR) on a B cell is known to enhance the level of both soluble CD23 and IgE, although the mechanism by which this occurs is not completely understood. In this study, we report that, in comparison with a CD40 ligand/IL-4-primed murine B cell alone, β2AR engagement on a primed B cell increased gene expression of a disintegrin and metalloproteinase (ADAM)10, which is the primary sheddase of CD23, as well as protein expression of both CD23 and ADAM10, in a protein kinase A- and p38 MAPK-dependent manner, and promoted the localization of these proteins to exosomes as early as 2 d after priming, as determined by both Western blot and flow cytometry and confirmed by electron microscopy. In comparison with isolated exosomes released from primed B cells alone, the transfer of exosomes released from β2AR agonist-exposed primed B cells to cultures of recipient primed B cells resulted in an increase in the level of IgE produced per cell, without affecting the number of cells producing IgE, as determined by ELISPOT. These effects still occurred when a β2AR antagonist was added along with the transfer to block residual agonist, and they failed to occur when exosomes were isolated from β2AR-deficient B cells. These findings suggest that the mechanism responsible for mediating the β2AR-induced increase in IgE involves a shuttling of the β2AR-induced increase in CD23 and ADAM10 proteins to exosomes that subsequently mediate an increase in IgE.
authors.affiliation: Biomedical Sciences Graduate Program, The Ohio State University Wexner College of Medicine, Columbus, OH 43210;
authors.forename: Caroline J
authors.initials: CJ
authors.lastname: Padro
authors.forename: Todd M
authors.initials: TM
authors.lastname: Shawler
authors.forename: Matthew G
authors.initials: MG
authors.lastname: Gormley
authors.forename: Virginia M
authors.initials: VM
authors.lastname: Sanders
mesh_terms: D051722:ADAM Proteins / Q000235:genetics / Q000378:metabolism*; D000072197:ADAM10 Protein; D058666:Adrenergic beta-2 Receptor Agonists / Q000494:pharmacology; D053829:Amyloid Precursor Protein Secretases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D002478:Cells, Cultured; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D055354:Exosomes / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology; D007073:Immunoglobulin E / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000187:drug effects; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D021381:Protein Transport; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics / Q000276:immunology; D017455:Receptors, IgE / Q000235:genetics / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D058666:Adrenergic beta-2 Receptor Agonists; D008565:Membrane Proteins; D018343:Receptors, Adrenergic, beta-2; D017455:Receptors, IgE; D007073:Immunoglobulin E; D017868:Cyclic AMP-Dependent Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D053829:Amyloid Precursor Protein Secretases; D051722:ADAM Proteins; D000072197:ADAM10 Protein; C491234:Adam10 protein, mouse