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Phorbol ester induces class II gene expression in pre-B cell lines.
P Sarthou1, E Jouvain-Marche, P A Cazenave
1Département d'Immunologie, Institut Pasteur, Paris, France.
European Journal of Immunology
|September 1, 1987
Summary
Phorbol myristate acetate (PMA) significantly enhances major histocompatibility complex class II (Ia) gene expression in pre-B cells. This induction occurs at the transcriptional level, suggesting protein kinase C activation plays a key role.
Area of Science:
- Immunology
- Molecular Biology
- Cell Biology
Background:
- Major histocompatibility complex (MHC) class II molecules are crucial for immune responses.
- Regulation of MHC class II expression in developing B cells is complex.
- Pre-B cell lines provide a model for studying B cell differentiation and gene regulation.
Purpose of the Study:
- To investigate the effect of phorbol myristate acetate (PMA) on MHC class II gene expression in Abelson murine leukemia virus-transformed pre-B cell lines.
- To elucidate the molecular mechanisms underlying PMA-induced MHC class II expression.
- To explore the role of protein kinase C (PKC) in regulating Ia molecule expression.
Main Methods:
- Treatment of pre-B cell lines with varying concentrations of PMA.
- Analysis of surface Ia molecule expression using flow cytometry.
- Assessment of gene transcription levels for Ia molecules.
- Derivation and characterization of a spontaneous Ia-positive variant cell line.
Main Results:
- Low concentrations of PMA (0.1-10 ng/ml) induced high levels of surface Ia molecules in three out of four cell lines.
- PMA-induced Ia expression was mediated at the transcriptional level.
- PMA triggered coordinated transcription of all four genes involved in Ia molecule biosynthesis.
- A derived Ia-positive variant showed increased sensitivity to PMA's toxic effects and high responsiveness to its Ia-inductive effects.
Conclusions:
- Phorbol myristate acetate (PMA) effectively induces major histocompatibility complex class II (Ia) gene expression in pre-B cells.
- The induction of Ia molecules by PMA is primarily regulated at the transcriptional level.
- Protein kinase C (PKC) activity, activated by phorbol esters like PMA, is a significant factor in controlling Ia molecule appearance and expression in pre-B cells.