Abstract
To determine the role of the pleiotropic cytokine TGF-beta in B cells, we generated mice lacking the TGF-beta receptor (TbetaR) type II selectively in this cell type through conditional mutagenesis (Cre/loxP). The absence of TbetaRII in B cells leads to a reduced life span of conventional B cells, expansion of peritoneal B-1 cells, B cell hyperplasia in Peyer's patches, elevated serum immunoglobulin, and substantial IgG3 responses to a normally weak immunogen. This B cell hyperresponsiveness is associated with a virtually complete serum IgA deficiency. The data reveal differential roles of TbetaR in homeostasis and antigen responsiveness of B cell subpopulations and establish a critical function of the TGF-beta receptor ligand pair in the induction of IgA responses in vivo.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antigens / administration & dosage
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B-Lymphocyte Subsets / immunology
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B-Lymphocyte Subsets / metabolism
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B-Lymphocyte Subsets / pathology
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B-Lymphocytes / immunology*
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B-Lymphocytes / metabolism*
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Cell Division / genetics
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Cell Division / immunology
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Chickens
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Crosses, Genetic
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Female
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Ficoll / administration & dosage
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Ficoll / immunology
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IgA Deficiency / genetics
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IgA Deficiency / immunology
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IgA Deficiency / pathology
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Immunoglobulin A / biosynthesis*
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Immunoglobulin Isotypes / biosynthesis
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Intestinal Mucosa / immunology
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Intestinal Mucosa / metabolism
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Intestinal Mucosa / pathology
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Lymphocyte Activation / genetics
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Mice
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Mice, Inbred BALB C
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Mice, Knockout
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Nitrophenols / administration & dosage
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Nitrophenols / immunology
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Peyer's Patches / immunology
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Peyer's Patches / metabolism
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Peyer's Patches / pathology
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Phenylacetates
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Protein Serine-Threonine Kinases
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Receptor, Transforming Growth Factor-beta Type II
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Receptors, Transforming Growth Factor beta / deficiency
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Receptors, Transforming Growth Factor beta / genetics
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Receptors, Transforming Growth Factor beta / physiology*
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Sequence Deletion
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gamma-Globulins / administration & dosage
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gamma-Globulins / immunology
Substances
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Antigens
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Immunoglobulin A
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Immunoglobulin Isotypes
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Nitrophenols
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Phenylacetates
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Receptors, Transforming Growth Factor beta
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gamma-Globulins
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4-hydroxy-5-nitrophenyl acetic acid
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Ficoll
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Protein Serine-Threonine Kinases
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Receptor, Transforming Growth Factor-beta Type II