Administration of an anti-IgE antibody inhibits CD23 expression and IgE production in vivo.
High IgE responder BDF1 mice were immunized intraperitoneally (i.p.) with dinitrophenol4 (DNP4)-ovalbumin (OVA) in alum concomitant with intravenous (i.v.) administration of an anti-IgE monoclonal antibody (mAb). IgE levels were undetectable in mice treated with the anti-IgE antibody, whereas mice treated with isotype-matched irrelevant mAb had IgE levels comparable to that of untreated, immunized mice. Subsequent antigen challenges with DNP4-OVA, either at weekly or monthly intervals, failed to evoke an IgE response for greater than 2 months in mice treated with anti-IgE during the primary sensitization, even though the terminal half-life of the anti-IgE antibody was 7 days. This inhibition was specific for DNP4-OVA since the DNP4-OVA-suppressed mice were able to respond to keyhole limpet haemocyanin (KLH). To investigate the effects of antibody treatment at the cellular level, passive transfer experiments were performed. The primary DNP-specific IgE response of adoptive transfer recipient mice was the same whether the donor cells were from mice treated with IgG or anti-IgE. Transfer of enriched T- or B-cell populations indicated that T-cell help was not compromised by administration of the anti-IgE mAb. However, splenocytes from the anti-IgE-treated mice failed to synthesize IgE in vitro, and flow cytometric analysis of B cells from anti-IgE-treated mice showed a dose-dependent decrease in CD23+ cells following antibody treatment, which correlated with decreased serum IgE levels. Taken together, the results of these studies suggest that anti-IgE treatment suppresses IgE responses via effects on B cells rather than T cells, possibly through effects on CD23-dependent pathways.
Haak-Frendscho
M
M
Department of Immunology, Genentech Inc., S. San Francisco, California 94080-4990.
Robbins
K
K
Lyon
R
R
Shields
R
R
Hooley
J
J
Schoenhoff
M
M
Jardieu
P
P
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000097:blood / Q000276:immunology; D000941:Antigens / Q000276:immunology; D004140:Dinitrophenols / Q000276:immunology; D006433:Hemocyanins / Q000276:immunology; D007073:Immunoglobulin E / Q000097:blood / Q000276:immunology*; D007074:Immunoglobulin G / Q000097:blood; D051379:Mice; D008815:Mice, Inbred Strains; D010047:Ovalbumin / Q000276:immunology; D017455:Receptors, IgE / Q000032:analysis*; D013154:Spleen / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology
D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D000941:Antigens; D004140:Dinitrophenols; D007074:Immunoglobulin G; D017455:Receptors, IgE; C045521:dinitrophenol-ovalbumin; D007073:Immunoglobulin E; D010047:Ovalbumin; D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin