Regulation of murine in vivo IgG and IgE responses by a monoclonal anti-IL-4 receptor antibody.
Although the cytokine interleukin 4 (IL-4) stimulates LPS-activated mouse B lymphocytes to secrete both IgG1 and IgE, an anti-IL-4 antibody completely inhibits IgE responses but has little or no effect on several in vivo IgG responses. IL-4 might, therefore, have a restricted role in the generation of in vivo humoral immune responses. Alternatively, IgG1 responses might be stimulated by IL-4 secreted by T cells that are interacting directly with B cells, so that anti-IL-4 antibody cannot neutralize IL-4 before it binds to a B cell IL-4 receptor. In contrast, an antibody that blocks the IL-4 receptor (IL-4R) should equally inhibit responses to IL-4 produced proximal to or distant from a B cell. This reasoning led us to determine the ability of an anti-IL-4R mAb to affect antibody production in mice injected with a goat antibody to mouse IgD (GaM delta) or inoculated with the nematode parasite Heligmosomoides polygyrus. Anti-IL-4R mAb, like anti-IL-4 mAb, blocked IgE responses by greater than 95% and enhanced IgG2a responses to a variable extent. Anti-IL-4R mAb, however, had only a modest and variable inhibitory effect on the induction of IgG1 responses, although it caused these responses to terminate more rapidly. A combination of anti-IL-4 and anti-IL-4R mAbs totally blocked goat anti-mouse IgD antibody (GaM delta)-induced IgE production but had no additive inhibitory effect on IgG1 production. These observations are most consistent with the view that IL-4 is required for a primary IgE response, but has relatively little role in the induction of IgG1 responses in the in vivo systems studied.
Finkelman
F D
FD
Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD 20814-4799.
Urban
J F
JF
Beckmann
M P
MP
Schooley
K A
KA
Holmes
J M
JM
Katona
I M
IM
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000096:biosynthesis; D000909:Antibodies, Helminth / Q000096:biosynthesis; D000911:Antibodies, Monoclonal; D001402:B-Lymphocytes / Q000276:immunology; D005260:Female; D007073:Immunoglobulin E / Q000096:biosynthesis*; D007074:Immunoglobulin G / Q000096:biosynthesis*; D015847:Interleukin-4 / Q000037:antagonists & inhibitors; D051379:Mice; D008807:Mice, Inbred BALB C; D009351:Nematospiroides dubius / Q000276:immunology; D019948:Receptors, Interleukin-4; D011975:Receptors, Mitogen / Q000037:antagonists & inhibitors*
D000888:Antibodies, Anti-Idiotypic; D000909:Antibodies, Helminth; D000911:Antibodies, Monoclonal; D007074:Immunoglobulin G; D019948:Receptors, Interleukin-4; D011975:Receptors, Mitogen; D015847:Interleukin-4; D007073:Immunoglobulin E