Germinal center B-cell-associated DNA hypomethylation at transcriptional regions of the AID gene.
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.
Fujimura
Satoru
S
Department of Immunology, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto 860-8556, Japan.
Matsui
Takeshi
T
Kuwahara
Kazuhiko
K
Maeda
Kazuhiko
K
Sakaguchi
Nobuo
N
D024506:5' Flanking Region; D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism*; D002454:Cell Differentiation; D002460:Cell Line; D003564:Cytidine Deaminase / Q000235:genetics / Q000378:metabolism*; D019175:DNA Methylation; D018858:Germinal Center / Q000166:cytology / Q000378:metabolism*; D015847:Interleukin-4 / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D010950:Plasma Cells / Q000378:metabolism; D010954:Plasmacytoma / Q000378:metabolism; D011401:Promoter Regions, Genetic; D013154:Spleen / Q000166:cytology; D053668:Syndecan-1 / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
D008070:Lipopolysaccharides; D053668:Syndecan-1; D015847:Interleukin-4; D000098830:AICDA (Activation-Induced Cytidine Deaminase); D003564:Cytidine Deaminase