IL-2 inhibits IL-4-dependent IgE and IgG1 production in vitro and in vivo.
Nippostrongylus brasiliensis (Nb) infection of mice induces IL-4 producing CD4+ T cells which stimulate polyclonal IgE and IgG1 production, providing a model system to study IL-4 action on B cells in vivo. B cell Ia expression and the proportion of IL-2R beta positive B cells were increased in Nb-inoculated mice, and B cells from these mice responded to IL-2 by prompt and marked cell growth. Injection of anti-IL-4 1 day after Nb inoculation substantially inhibited these responses, indicating that they were largely IL-4 dependent. Thus IL-4 acted as a polyclonal B cell activator in vivo and caused B cells to develop into IL-2 responsive cells. Furthermore, injection of IL-2 inhibited IgG1 and IgE production by Nb-inoculated mice. To understand the mechanism of this IL-2-mediated inhibition, we used an in vitro IgG1 and IgE induction system. B cells from Nb-inoculated mice displayed an increase in the capacity of IL-2 to inhibit lipopolysaccharide (LPS) plus IL-4-driven IgE and IgG1 production, indicating that B cells expressing IL-2R beta are highly sensitive to IL-2. This inhibition was principally dependent upon the direct action of IL-2 on B cells. However, partial abolition of IL-2 inhibitory action by anti-IFN-gamma treatment suggested that endogenous IFN-gamma released from IL-2-stimulated cells was also involved in this IL-2-mediated IgE and IgG1 inhibition. Northern blot analysis demonstrated that IL-2 inhibited IL-4 induction of germline and productive C epsilon transcripts in LPS-stimulated B cells. Digestion-circularization polymerase chain reaction analysis revealed IL-2 inhibited IL-4 induction of s mu-s gamma 1 rearrangement in LPS-stimulated B cells.
Nakanishi
K
K
Department of Immunology and Medical Zoology, Hyogo College of Medicine, Japan.
Yoshimoto
T
T
Chu
C C
CC
Matsumoto
H
H
Hase
K
K
Nagai
N
N
Tanaka
T
T
Miyasaka
M
M
Paul
W E
WE
Shinka
S
S
D000818:Animals; D000909:Antibodies, Helminth / Q000096:biosynthesis*; D001402:B-Lymphocytes / Q000276:immunology; D015152:Blotting, Northern; D005260:Female; D005434:Flow Cytometry; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis; D007073:Immunoglobulin E / Q000096:biosynthesis*; D007074:Immunoglobulin G / Q000096:biosynthesis*; D007376:Interleukin-2 / Q000502:physiology*; D015847:Interleukin-4 / Q000037:antagonists & inhibitors*; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D009559:Nippostrongylus / Q000276:immunology; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000096:biosynthesis; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis; D017206:Strongylida Infections / Q000276:immunology
D000909:Antibodies, Helminth; D000949:Histocompatibility Antigens Class II; D007074:Immunoglobulin G; D007376:Interleukin-2; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D015375:Receptors, Interleukin-2; D015847:Interleukin-4; D007073:Immunoglobulin E