Insulin-like growth factor-1 controls type 2 T cell-independent B cell response.
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.
Baudler
Stephanie
S
Institute for Genetics, University of Cologne, Germany.
Baumgartl
Julia
J
Hampel
Brigitte
B
Buch
Thorsten
T
Waisman
Ari
A
Snapper
Clifford M
CM
Krone
Wilhelm
W
Brüning
Jens C
JC
D000818:Animals; D000955:Antigens, T-Independent / Q000276:immunology* / Q000378:metabolism*; D016175:B-Lymphocyte Subsets / Q000166:cytology / Q000201:enzymology / Q000276:immunology* / Q000378:metabolism*; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D015536:Down-Regulation / Q000235:genetics / Q000276:immunology; D016332:Fetal Tissue Transplantation / Q000276:immunology; D005362:Ficoll / Q000008:administration & dosage / Q000276:immunology; D007136:Immunoglobulins / Q000096:biosynthesis; D007334:Insulin-Like Growth Factor I / Q000378:metabolism / Q000502:physiology*; D016031:Liver Transplantation / Q000276:immunology; D008213:Lymphocyte Activation / Q000235:genetics; D038041:Lymphopoiesis / Q000235:genetics / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009596:Nitrophenols / Q000008:administration & dosage / Q000276:immunology; D010648:Phenylacetates; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000378:metabolism; D011828:Radiation Chimera / Q000276:immunology; D017526:Receptor, IGF Type 1 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D015854:Up-Regulation / Q000235:genetics / Q000276:immunology
D000955:Antigens, T-Independent; D007136:Immunoglobulins; D009596:Nitrophenols; D010648:Phenylacetates; C026242:4-hydroxy-5-nitrophenyl acetic acid; D019000:Phosphotyrosine; D005362:Ficoll; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1