Methylation of an immediate-early inducible gene as a mechanism for B cell tolerance induction.
Stage-specific gene regulation is important in determining cell function during development. Immature B cells expressing membrane-bound immunoglobulin M (mIgM) are sensitive to antigen-induced tolerance, whereas mature B cells are activated by antigen. Previous studies have established an association between Egr-1 gene induction and antigen receptor (mIgM)-mediated activation of mature B cells. Here it is shown that the immature B cell line WEHI-231 and tolerance-sensitive bone marrow-derived B cells do not express Egr-1. It is further shown that lack of inducible expression in these cells is due to specific methylation of the Egr-1 gene. Thus, covalent inactivation of an activation-associated gene may explain tolerance sensitivity at specific stages of B cell development.
Seyfert
V L
VL
Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia 19104-6084.
McMahon
S B
SB
Glenn
W D
WD
Yellen
A J
AJ
Sukhatme
V P
VP
Cao
X M
XM
Monroe
J G
JG
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D015139:Blotting, Southern; D002460:Cell Line; D004247:DNA / Q000378:metabolism*; D005786:Gene Expression Regulation; D007108:Immune Tolerance; D007075:Immunoglobulin M / Q000276:immunology; D008745:Methylation; D051379:Mice; D011401:Promoter Regions, Genetic; D015183:Restriction Mapping; D014158:Transcription, Genetic; D015533:Transcriptional Activation
D007075:Immunoglobulin M; D004247:DNA