IL-21 effects on human IgE production in response to IL-4 or IL-13.
In human atopic disease, IgE sensitizes the allergic response, while IgG4 is protective. Because IL-4 and IL-13 trigger switch recombination to both IgE and IgG4, additional agents must regulate the balance between these isotypes to influence susceptibility or tolerance to atopy. In this report, we define in vitro conditions leading to activation or inhibition of human IgE and IgG4 production by IL-21. IL-21 reduced IL-4-driven IgE synthesis by mitogen-stimulated human PBMC. IL-21 inhibition of human IgE production was not a direct effect on B cells, was not seen following B cell activation with IL-13, and was overcome by CD40 ligation. Neither IFN-gamma, IL-10, IL-12, CD40L expression, nor apoptosis was responsible for the inhibitory effect. In contrast, IL-21-stimulated secretion of IgG4 from PBMC. Our findings indicate that IL-21 may influence the production of both human IgE and IgG4, and thus contribute to the regulation of atopic reactions.
Wood
Nancy
N
Wyeth Research, Cambridge, MA, USA.
Bourque
Karen
K
Donaldson
Debra D
DD
Collins
Mary
M
Vercelli
Donata
D
Goldman
Samuel J
SJ
Kasaian
Marion T
MT
D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001402:B-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D019013:CD40 Antigens / Q000276:immunology; D023201:CD40 Ligand / Q000276:immunology / Q000378:metabolism; D049109:Cell Proliferation; D002478:Cells, Cultured; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007073:Immunoglobulin E / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology*; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000276:immunology; D007371:Interferon-gamma / Q000235:genetics; D016753:Interleukin-10 / Q000096:biosynthesis; D018664:Interleukin-12 / Q000096:biosynthesis; D018793:Interleukin-13 / Q000276:immunology* / Q000494:pharmacology; D015847:Interleukin-4 / Q000276:immunology* / Q000494:pharmacology; D007378:Interleukins / Q000276:immunology* / Q000494:pharmacology; D018123:Receptors, Interleukin / Q000096:biosynthesis / Q000378:metabolism; D053707:Receptors, Interleukin-12; D000098546:Interleukin-21
D000911:Antibodies, Monoclonal; D019013:CD40 Antigens; D007074:Immunoglobulin G; D018793:Interleukin-13; D007378:Interleukins; D018123:Receptors, Interleukin; D053707:Receptors, Interleukin-12; D016753:Interleukin-10; D023201:CD40 Ligand; D018664:Interleukin-12; D015847:Interleukin-4; D007073:Immunoglobulin E; D007371:Interferon-gamma; D000098546:Interleukin-21