title: Transgenic overexpression of G5PR that is normally augmented in centrocytes impairs the enrichment of high-affinity antigen-specific B cells, increases peritoneal B-1a cells, and induces autoimmunity in aged female mice.
abstract: To investigate signals that control B cell selection, we examined expression of G5PR, a regulatory subunit of the serine/threonine protein phosphatase 2A, which suppresses JNK phosphorylation. G5PR is upregulated in activated B cells, in Ki67-negative centrocytes at germinal centers (GCs), and in purified B220(+)Fas(+)GL7(+) mature GC B cells following Ag immunization. G5PR rescues transformed B cells from BCR-mediated activation-induced cell death by suppression of late-phase JNK activation. In G5PR-transgenic (G5PR(Tg)) mice, G5PR overexpression leads to an augmented generation of GC B cells via an increase in non-Ag-specific B cells and a consequent reduction in the proportion of Ag-specific B cells and high-affinity Ab production after immunization with nitrophenyl-conjugated chicken γ-globulin. G5PR overexpression impaired the affinity-maturation of Ag-specific B cells, presumably by diluting the numbers of high-affinity B cells. However, aged nonimmunized female G5PR(Tg) mice showed an increase in the numbers of peritoneal B-1a cells and the generation of autoantibodies. G5PR overexpression did not affect the proliferation of B-1a and B-2 cells but rescued B-1a cells from activation-induced cell death in vitro. G5PR might play a pivotal role in B cell selection not only for B-2 cells but also for B-1 cells in peripheral lymphoid organs.
authors: Department of Immunology, Graduate School of Life Sciences, Kumamoto University, Kumamoto 860-8556, Japan.
authors: Masahiro
authors: M
authors: Kitabatake
authors: Teppei
authors: T
authors: Toda
authors: Kazuhiko
authors: K
authors: Kuwahara
authors: Hideya
authors: H
authors: Igarashi
authors: Mareki
authors: M
authors: Ohtsuji
authors: Hiromichi
authors: H
authors: Tsurui
authors: Sachiko
authors: S
authors: Hirose
authors: Nobuo
authors: N
authors: Sakaguchi
mesh_terms: D000375:Aging / Q000276:immunology*; D000818:Animals; D001327:Autoimmune Diseases / Q000201:enzymology / Q000235:genetics / Q000276:immunology*; D016175:B-Lymphocyte Subsets / Q000201:enzymology / Q000276:immunology* / Q000473:pathology; D002645:Chickens; D018985:Epitopes, B-Lymphocyte / Q000276:immunology*; D005260:Female; D018858:Germinal Center / Q000166:cytology / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008814:Mice, Inbred NZB; D008822:Mice, Transgenic; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000502:physiology; D010529:Peritoneal Cavity / Q000166:cytology; D010749:Phosphoprotein Phosphatases / Q000096:biosynthesis / Q000235:genetics* / Q000502:physiology; D021122:Protein Subunits / Q000096:biosynthesis / Q000235:genetics* / Q000502:physiology; D051381:Rats; D011917:Rats, Inbred Lew; D012727:Sex Characteristics; D015854:Up-Regulation / Q000235:genetics / Q000276:immunology*
chemical_list: D018985:Epitopes, B-Lymphocyte; D009687:Nuclear Proteins; D021122:Protein Subunits; D010749:Phosphoprotein Phosphatases; C089641:protein phosphatase 5