Abstract
The IGF-1 receptor (IGF-1R) is expressed on T and B lymphocytes, and the expression of the insulin- and IGF-1-signaling machinery undergoes defined changes throughout lineage differentiation, offering a putative role for IGF-1 in the regulation of immune responses. To study the role of the IGF-1R in lymphocyte differentiation and function in vivo, we have reconstituted immunodeficient RAG2-deficient mice with IGF-1R(-/-) fetal liver cells. Despite the absence of IGF-1Rs, the development and ex vivo activation of B and T lymphocytes were unaltered in these chimeric mice. By contrast, the humoral immune response to the T cell-independent type 2 Ag 4-hydroxy-3-nitrophenyl acetyl-Ficoll was significantly reduced in mice reconstituted with IGF-1R-deficient fetal liver cells, whereas responses to the T cell-dependent Ag 4-hydroxy-3-nitrophenyl acetyl-chicken globulin were normal. Moreover, in an in vitro model of T cell-independent type 2 responses, IGF-1 promoted Ig production potently upon polyvalent membrane-IgD cross-linking. These data indicate that functional IGF-1R signaling is required for T cell-independent B cell responses in vivo, defining a novel regulatory mechanism for the immune response against bacterial polysaccharides.
MeSH terms
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Animals
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Antigens, T-Independent / immunology*
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Antigens, T-Independent / metabolism*
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B-Lymphocyte Subsets / cytology
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B-Lymphocyte Subsets / enzymology
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B-Lymphocyte Subsets / immunology*
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B-Lymphocyte Subsets / metabolism*
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Cell Differentiation / genetics
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Cell Differentiation / immunology
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Down-Regulation / genetics
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Down-Regulation / immunology
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Fetal Tissue Transplantation / immunology
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Ficoll / administration & dosage
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Ficoll / immunology
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Immunoglobulins / biosynthesis
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Insulin-Like Growth Factor I / metabolism
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Insulin-Like Growth Factor I / physiology*
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Liver Transplantation / immunology
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Lymphocyte Activation / genetics
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Lymphopoiesis / genetics
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Lymphopoiesis / immunology
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Nitrophenols / administration & dosage
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Nitrophenols / immunology
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Phenylacetates
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Phosphorylation
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Phosphotyrosine / metabolism
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Radiation Chimera / immunology
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Receptor, IGF Type 1 / deficiency
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Receptor, IGF Type 1 / genetics
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Receptor, IGF Type 1 / physiology*
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Signal Transduction / genetics
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Signal Transduction / immunology
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T-Lymphocytes / cytology
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T-Lymphocytes / immunology
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T-Lymphocytes / metabolism
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Up-Regulation / genetics
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Up-Regulation / immunology
Substances
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Antigens, T-Independent
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Immunoglobulins
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Nitrophenols
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Phenylacetates
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4-hydroxy-5-nitrophenyl acetic acid
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Phosphotyrosine
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Ficoll
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Insulin-Like Growth Factor I
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Receptor, IGF Type 1