International Immunology, Vol. 13, No. 5, 705-710,
May 2001
© 2001 Japanese Society for Immunology
Regulation of CD21 expression by DNA methylation and histone deacetylation
1 Immunology, Department of Biology, Faculty of Sciences, University of Konstanz, M662, 78457 Konstanz, Germany
2 Biotechnologie Institut Thurgau, Konstanzerstrasse 19, 8274 Tägerwilen, Switzerland
Correspondence to: H. Illges, Immunology, Department of Biology, Faculty of Sciences, University of Konstanz, M662, 78457 Konstanz, Germany
The complement receptor II (CD21) serves as a receptor for the complement component C3d of immune complexes on B lymphocytes. Expression of the CD21 gene is tightly regulated during B lymphocyte differentiation. Only mature B lymphocytes, but not pro-, pre- or plasma B lymphocytes, express CD21. There is evidence that cell type-specific expression is mediated by a silencer element located in the first intron. The CD21 promoter region contains a CpG island adjacent to the ATG start codon. We have analyzed the methylation status of this CpG island in B lymphoid cell lines representing the various differentiation stages of B lymphocyte development and primary lymphocytes. We found that the pro-, pre- and intermediate B lymphocytes contain a methylated CpG island and do not express CD21, whereas CD21-expressing mature B lymphocytes, plasma B lymphocytes and non-lymphoid cells carry a demethylated CD21 CpG island. To analyze whether the lack of CD21 expression in early B lymphocytes is due to inhibition by CpG methylation we have used 5-aza-2'-deoxycytidine to inhibit DNA methyltransferase activity. Treatment of pro-B lymphocytes with the drug resulted in expression of CD21. We have also applied Trichostatin A (TSA), an inhibitor of histone deacetylation, to determine whether the state of histone deacetylation affects the expression of CD21. We found that TSA induces expression of CD21 in early B lymphocytes. Thus CD21 expression is controlled by both methylation of the CD21 CpG island and chromatin modification through histone deacetylation in early B lymphocyte development.
Keywords: B lymphocyte, chromatin, complement receptor II, CR2, differentiation
Transmitting editor: A. Radbruch
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