Enhancer mediated suppression of epsilon heavy-chain gene expression in a murine IgE-producing hybridoma

Keats Nelms, Brian G. Van Ness, Richard G. Lynch, Ambika Mathur

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9 Scopus citations

Abstract

In vitro co-culture of IgE-secreting hybridoma cells (B53) with spleen cells harvested from mice with established B53 tumours results in a specific, T cell-dependent suppression of ε{lunate}-chain expression in the B53 cells. The role of immunoglobulin enhancers in the suppression of IgE synthesis in B53 cells was examined by transfecting B53 cells with CAT expression vectors containing the immunoglobulin heavy or kappa light-chain intron enhancers or a Rous sarcoma virus (RSV) LTR. When ε{lunate}-chain expression of transfected cells was suppressed in vitro, CAT expression was also suppressed in cells transfected with vectors containing the immunoglobulin heavy-chain gene enhancer, but not in cells transfected with vectors containing the kappa enhancer or RSV LTR. Thus, the T cell-dependent suppression of IgE synthesis in B53 cells correlates with a specific inactivation of the immunoglobulin heavy chain enhancer, strongly suggesting that T cell-mediated suppression of Ig synthesis can normally occur through specific repression of Ig enhancer function. This represents a new regulatory pathway involved in the control of IgE synthesis and is the first indication that the enhancer mediated expression of Ig genes in B cells can be modulated through T cell-dependent processes.

Original languageEnglish (US)
Pages (from-to)599-606
Number of pages8
JournalMolecular Immunology
Volume28
Issue number6
DOIs
StatePublished - Jun 1991

Bibliographical note

Funding Information:
Acknowledgements-We are grateful to Drs Michael Lenardo and Howard Towle for generously providing plasmids and to Marita Robinson, Che-Leung Law and Dr Tucker LeBien for assistance in the flow cytometry studies and FACScan use. We are also grateful to Drs Kathleen Conklin, Harry Orr, and Bruce Blazar for their helpful comments. This work was supported in part by NIH grants CA49228 to R.G.L. and GM37687 to B.V.N.

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