Document Detail


Inhibition of B cell proliferation by antisense DNA to both alpha and beta forms of Fc epsilon R II.
MedLine Citation:
PMID:  1327538     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Epstein-Barr Virus (EBV) infection activates B lymphocyte proliferation through partially understood mechanisms, resulting in phenotypic changes, including the appearance of new antigens. One such antigen is Fc epsilon R II/CD-23 which may be relevant for B cell proliferation. We have used anti-sense oligonucleotides to study the importance of the two forms of this molecule for proliferation in the EBV-transformed, Fc epsilon R II +ve lymphoblastoid B cell line, RPMI 8866. Anti-sense oligodeoxynucleotides were generated to the two forms of Fc epsilon R II; Fc epsilon R IIa (alpha) and IIb (beta) which differ only in their intracytoplasmic domains. Addition of increasing concentrations of anti-sense oligonucleotides, ranging from 1 to 30 microM, significantly decreased cellular proliferation as measured by the incorporation of [3H]thymidine (inhibition range 8-88%). Optimum inhibition of cellular proliferation was apparent at 15 microM concentration of both anti-sense Fc epsilon R IIa and IIb (Fc epsilon R IIa, mean +/- SE = 75 +/- 7% inhibition, p less than 0.001; Fc epsilon R IIb, mean +/- SE = 71 +/- 7% inhibition, p less than 0.001). Anti-sense oligonucleotides complementary to the common part of Fc epsilon R II resulted in a similar inhibition of proliferation. Sense oligonucleotides did not induce significant inhibition. Preincubation of sense and anti-sense oligonucleotides resulted in an abrogation of proliferation inhibition. Moreover, none of these oligonucleotides had any effect on a Fc epsilon R II -ve cell line. Incubation with both anti-sense IIa and IIb resulted in additive, but not synergistic inhibition of proliferation. Addition of soluble Fc epsilon R II did not reverse inhibition of proliferation, suggesting that membrane-bound or intracellular rather than soluble Fc epsilon R II was important for the induced proliferation. Analysis of cell surface expression for Fc epsilon II indicated that while there was a pronounced effect on cell number following incubation with anti-sense oligonucleotides, surface expression of Fc epsilon R II was consistent as measured over different time points. PCR analysis revealed that while most cells expressed either the alpha or the beta form of Fc epsilon R II, EBV-transformed cell lines, particularly RPMI 8866, were found to express both alpha and beta forms simultaneously. This may constitute a mechanism whereby EBV infection confers an immortal state to the cell, resulting in its uncontrolled proliferation. Cell lines expressing only one receptor form, either alpha or beta, were unaffected after incubation with anti-sense oligonucleotides.(ABSTRACT TRUNCATED AT 400 WORDS)
Authors:
L Bhatti; K Behle; R H Stevens
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Cellular immunology     Volume:  144     ISSN:  0008-8749     ISO Abbreviation:  Cell. Immunol.     Publication Date:  1992 Oct 
Date Detail:
Created Date:  1992-10-28     Completed Date:  1992-10-28     Revised Date:  2001-11-02    
Medline Journal Info:
Nlm Unique ID:  1246405     Medline TA:  Cell Immunol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  117-30     Citation Subset:  IM    
Affiliation:
Department of Microbiology and Immunology, University of California, Los Angeles 90024-1747.
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MeSH Terms
Descriptor/Qualifier:
B-Lymphocytes / drug effects*
Base Sequence
Cell Division / drug effects
Cell Line, Transformed
DNA, Antisense / pharmacology*
Dose-Response Relationship, Drug
Herpesvirus 4, Human
Interleukin-4 / pharmacology
Molecular Sequence Data
Receptors, IgE / drug effects*,  genetics,  immunology*
Up-Regulation
Chemical
Reg. No./Substance:
0/DNA, Antisense; 0/Receptors, IgE; 207137-56-2/Interleukin-4

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