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

Masahiro Kitabatake, Teppei Toda, Kazuhiko Kuwahara, Hideya Igarashi, Mareki Ohtsuji, Hiromichi Tsurui, Sachiko Hirose, Nobuo Sakaguchi

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)

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 G5PRtransgenic (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.

Original languageEnglish
Pages (from-to)1193-1201
Number of pages9
JournalJournal of Immunology
Volume189
Issue number3
DOIs
Publication statusPublished - 01-08-2012
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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