TGF-beta receptor controls B cell responsiveness and induction of IgA in vivo.
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.
Cazac
B B
BB
Department of Medicine, The Windeyer Institute of Medical Sciences, University College, London, United Kingdom.
Roes
J
J
D000818:Animals; D000941:Antigens / Q000008:administration & dosage; D016175:B-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D002455:Cell Division / Q000235:genetics / Q000276:immunology; D002645:Chickens; D003433:Crosses, Genetic; D005260:Female; D005362:Ficoll / Q000008:administration & dosage / Q000276:immunology; D017098:IgA Deficiency / Q000235:genetics / Q000276:immunology / Q000473:pathology; D007070:Immunoglobulin A / Q000096:biosynthesis*; D007132:Immunoglobulin Isotypes / Q000096:biosynthesis; D007413:Intestinal Mucosa / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008213:Lymphocyte Activation / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D009596:Nitrophenols / Q000008:administration & dosage / Q000276:immunology; D010581:Peyer's Patches / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D010648:Phenylacetates; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D017384:Sequence Deletion; D005719:gamma-Globulins / Q000008:administration & dosage / Q000276:immunology
D000941:Antigens; D007070:Immunoglobulin A; D007132:Immunoglobulin Isotypes; D009596:Nitrophenols; D010648:Phenylacetates; D018125:Receptors, Transforming Growth Factor beta; D005719:gamma-Globulins; C026242:4-hydroxy-5-nitrophenyl acetic acid; D005362:Ficoll; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II