TGF-beta Receptor Controls B Cell Responsiveness and Induction of IgA in Vivo

Immunity. 2000 Oct;13(4):443-51. doi: 10.1016/s1074-7613(00)00044-3.

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

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens / administration & dosage
  • B-Lymphocyte Subsets / immunology
  • B-Lymphocyte Subsets / metabolism
  • B-Lymphocyte Subsets / pathology
  • B-Lymphocytes / immunology*
  • B-Lymphocytes / metabolism*
  • Cell Division / genetics
  • Cell Division / immunology
  • Chickens
  • Crosses, Genetic
  • Female
  • Ficoll / administration & dosage
  • Ficoll / immunology
  • IgA Deficiency / genetics
  • IgA Deficiency / immunology
  • IgA Deficiency / pathology
  • Immunoglobulin A / biosynthesis*
  • Immunoglobulin Isotypes / biosynthesis
  • Intestinal Mucosa / immunology
  • Intestinal Mucosa / metabolism
  • Intestinal Mucosa / pathology
  • Lymphocyte Activation / genetics
  • Mice
  • Mice, Inbred BALB C
  • Mice, Knockout
  • Nitrophenols / administration & dosage
  • Nitrophenols / immunology
  • Peyer's Patches / immunology
  • Peyer's Patches / metabolism
  • Peyer's Patches / pathology
  • Phenylacetates
  • Protein-Serine-Threonine Kinases
  • Receptor, Transforming Growth Factor-beta Type II
  • Receptors, Transforming Growth Factor beta / deficiency
  • Receptors, Transforming Growth Factor beta / genetics
  • Receptors, Transforming Growth Factor beta / physiology*
  • Sequence Deletion
  • gamma-Globulins / administration & dosage
  • gamma-Globulins / immunology

Substances

  • Antigens
  • Immunoglobulin A
  • Immunoglobulin Isotypes
  • Nitrophenols
  • Phenylacetates
  • Receptors, Transforming Growth Factor beta
  • gamma-Globulins
  • 4-hydroxy-5-nitrophenyl acetic acid
  • Ficoll
  • Protein-Serine-Threonine Kinases
  • Receptor, Transforming Growth Factor-beta Type II