Inhibition of immunoglobulin E synthesis through Fc gammaRII (CD32) by a mechanism independent of B-cell receptor co-cross-linking.
The inhibitory effect on antibody production by immune complexes has been shown to depend on co-ligation of the B-cell antigen receptor (BCR) with the low-affinity receptor for immunoglobulin G (IgG) (Fc gammaRIIb, CD32). Here we report that immunoglobulin E (IgE) synthesis, induced in a BCR-independent manner by interleukin-4 (IL-4) and anti-CD40 antibody, was inhibited by CD32 ligation. The observed effect was specific for CD32 as, first, antibodies directed against other B-cell surface structures had no inhibitory effect, and, second, treatment with anti-CD32 of cells that had been in culture for 2 days was ineffective owing to the down-regulation of CD32 expression. IgE inhibition was also observed in cells stimulated by IL-4/CD40 F(ab')(2) or IL-4 plus soluble CD40 ligand, demonstrating that co-cross-linking of CD32 and CD40 was not necessary to induce inhibition. Mechanistic studies into the IgE class switch process demonstrated that IL-4/anti-CD40-induced IgE germline gene transcription and B-cell proliferation were not affected by CD32 ligation. The data demonstrate that the negative regulatory role of the CD32 molecule is not restricted to BCR-induced B-cell activation, but is also functional on other B-cell activation pathways mediated by CD40 and IL-4.
Horejs-Hoeck
Jutta
J
University of Salzburg, Salzburg, Austria.
Hren
Andrea
A
Mudde
Geert C
GC
Woisetschläger
Maximilian
M
D000918:Antibody Specificity / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D019013:CD40 Antigens / Q000276:immunology; D002455:Cell Division / Q000276:immunology; D002460:Cell Line; D002478:Cells, Cultured; D015536:Down-Regulation / Q000276:immunology; D006801:Humans; D007070:Immunoglobulin A / Q000096:biosynthesis; D007073:Immunoglobulin E / Q000096:biosynthesis*; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000276:immunology; D007132:Immunoglobulin Isotypes / Q000276:immunology; D007075:Immunoglobulin M / Q000096:biosynthesis; D015847:Interleukin-4 / Q000276:immunology; D008024:Ligands; D014066:Palatine Tonsil / Q000276:immunology; D011947:Receptors, Antigen, B-Cell / Q000276:immunology*; D017452:Receptors, IgG / Q000276:immunology*; D014158:Transcription, Genetic / Q000276:immunology
D019013:CD40 Antigens; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007132:Immunoglobulin Isotypes; D007075:Immunoglobulin M; D008024:Ligands; D011947:Receptors, Antigen, B-Cell; D017452:Receptors, IgG; D015847:Interleukin-4; D007073:Immunoglobulin E