Biomedical subjects

D M Zaller

Publications and source records attributed to D M Zaller.

20 records · Page 2Linked to original sources

PubMed1988

Genes activated in the presence of an immunoglobulin enhancer or promoter are negatively regulated by a T-lymphoma cell line.

The tissue-specific expression of immunoglobulin genes can be partially explained by a requirement for activating factors found only in B lymphocytes and their derivatives. However, loss of immunoglobulin expression upon fusion of an immunoglobulin-producing myeloma cell with a T lymphoma cell (BW5147) or fibroblast (L cell) suggests that negatively acting factors also play a role in the tissue specificity of immunoglobulin genes. Expression of a cloned immunoglobulin heavy-chain gene introduced into myeloma cells was suppressed after fusion of the myeloma transformants with BW5147. The presence of either the immunoglobulin heavy-chain enhancer or promoter conferred suppression, under similar conditions, upon a heterologous gene that is normally expressed in both B and T lymphocytes. These immunoglobulin heavy-chain gene control regions, or gene modifications induced by them, are subject to negative control by T-lymphocyte-derived factors.

Animals↗

PubMed1985

Deletion of a B-cell-specific enhancer affects transfected, but not endogenous, immunoglobulin heavy-chain gene expression.

A transcriptional enhancer has recently been identified between the variable and constant region coding segments of an assembled immunoglobulin heavy-chain gene. This enhancer is required for efficient expression of such genes when transfected into myeloma cells. A class switch rearrangement in the mouse myeloma cell line 9.9.2.1 has resulted in deletion of this enhancer, and yet this cell line continues to produce heavy chains at a high level. Cell line 9.9.2.1 is a gamma 2a-producing class-switch variant derived from the gamma 2b-producing myeloma cell line, MPC11. We demonstrate that despite the high level of heavy-chain production in 9.9.2.1, the cloned 9.9.2.1 heavy-chain gene is not expressed efficiently when transfected into myeloma cells. Efficient expression after transfection can be obtained only if the deleted enhancer is reinserted into the gene. The implication of this finding for the role of this enhancer in establishing and/or maintaining immunoglobulin heavy-chain gene expression is discussed.

Animals↗