Germinal center B-cell-associated DNA hypomethylation at transcriptional regions of the AID gene

Satoru Fujimura, Takeshi Matsui, Kazuhiko Kuwahara, Kazuhiko Maeda, Nobuo Sakaguchi

Research output: Contribution to journalArticlepeer-review

16 Citations (Scopus)

Abstract

T-cell-dependent antigen induces differentiation of germinal center (GC) B-cell in peripheral lymphoid follicles. We studied whether GC B-cell differentiation is associated with DNA methylation status by examining regulatory regions of mouse AID transcription that are essential for B-cell maturation. AID-negative cell lines of pre-B cells, immature B cells, mature B cells, plasmacytomas or T cells showed various hypermethylation profiles in the 5′-promoter and intronic regions. In contrast, AID-positive GC-type B cells were hypomethylated in these regions. Stimulation of splenic B cells with lipopolysaccharide and interleukin-4 caused DNA hypomethylation in the 5′-promoter and intronic CpG sites proportional to the increase in AID transcription. Mature GL7+Fas+ GC B cells were hypomethylated at these CpG sites, especially near the Pax5-consensus site and an intronic site. However, Syndecan-1+ plasma cells showed DNA hypermethylation, as seen in plasmacytomas. Methylation status of the transcriptional regulatory region might contribute to stage-dependent activation of AID transcription during GC B-cell differentiation.

Original languageEnglish
Pages (from-to)1712-1719
Number of pages8
JournalMolecular Immunology
Volume45
Issue number6
DOIs
Publication statusPublished - 01-03-2008
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Immunology
  • Molecular Biology

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