Activation of terminal B cell differentiation by inhibition of histone deacetylation.
Mol Immunol
; 39(15): 923-32, 2003 May.
Article
in En
| MEDLINE
| ID: mdl-12695118
ABSTRACT
A role for histone acetylation, which can alter the accessibility of DNA to transcriptional regulatory proteins and contribute to gene expression, in regulating terminal B cell differentiation was investigated in the mature B lymphoma L10A and mouse splenic B cells. Incubation of the L10A cells with the histone deacetylase (HDAC) inhibitors trichostatin A (TSA) and butyrate increased expression of Blimp-1, J chain, and mad genes, decreased expression of c-myc and BSAP/Pax-5 genes, increased the expression of surface CD43 and Syndecan-1, and decreased surface IgM. Incubation of splenic B cells with TSA and dextran conjugated anti-IgD Ab increased Blimp-1 gene and Syndecan-1 surface expression. The alteration in gene expression and cell surface markers was consistent with induction of the onset of terminal B cell differentiation. Co-incubation of L10A cells with TSA and cycloheximide (CHX) abrogated the up-regulation of Blimp-1 expression, indicating that TSA-activated Blimp-1 expression required synthesis of a transcriptional activator. In contrast, mad expression was increased in L10A cells cultured with TSA and cycloheximide or cycloheximide alone, suggesting mad expression may occur independent of Blimp-1 expression and is regulated by a labile, HDAC associated transcriptional repressor. The results demonstrate that histone acetylation regulates transcription of genes controlling terminal B cell differentiation.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
B-Lymphocytes
/
Antigens, CD
/
Histone Deacetylase Inhibitors
Type of study:
Prognostic_studies
Limits:
Animals
Language:
En
Journal:
Mol Immunol
Year:
2003
Document type:
Article
Affiliation country:
United States