Abstract

The transition from the expression of surface immunoglobulin to the active secretion of antibody marks the ultimate stage in the differentiation of B lymphocytes. This transition is reflected in the virtually exclusive expression of secreted mu (mus) mRNA over membrane mu (mum) and delta mRNAs. Stage-specific termination of transcription between the C mu and C delta gene segments is known to be the mechanism which controls delta heavy chain expression in terminally differentiated antibody- secreting cells. Our studies now indicate that the sequences involved in stage-specific transcription termination are closely linked to the membrane mu sequences involved in the polyadenylation of mum mRNA. This proposal is directed at determining the elements and mechanisms involved in stage- specific transcription termination in the mu and delta complex transcription unit. The close proximity of the region of stage- specific termination to the signals for mum mRNA polyadenylation may reflect a linkage of these processes involved in regulating B lymphocyte maturation.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
1R01GM040185-01
Application #
3297563
Study Section
Allergy and Immunology Study Section (ALY)
Project Start
1988-04-01
Project End
1993-03-31
Budget Start
1988-04-01
Budget End
1989-03-31
Support Year
1
Fiscal Year
1988
Total Cost
Indirect Cost

  Institution

Name
University of California Los Angeles
Department
Type
Schools of Medicine
DUNS #
119132785
City
Los Angeles
State
CA
Country
United States
Zip Code
90095

  Publications

Henson, Sarah E; Morford, Travis; Stein, Mary-Pat et al. (2011) Candidate genes contributing to the aggressive phenotype of mantle cell lymphoma. Acta Histochem 113:729-42
Kuraishy, Ali I; French, Samuel W; Sherman, Mara et al. (2007) TORC2 regulates germinal center repression of the TCL1 oncoprotein to promote B cell development and inhibit transformation. Proc Natl Acad Sci U S A 104:10175-80
Malone, Cindy S; Kuraishy, Ali I; Fike, Francesca M et al. (2006) B29 gene silencing in pituitary cells is regulated by its 3' enhancer. J Mol Biol 362:173-83
Henson, Sarah E; Tsai, Shih-Chang; Malone, Cindy Sue et al. (2006) Pir51, a Rad51-interacting protein with high expression in aggressive lymphoma, controls mitomycin C sensitivity and prevents chromosomal breaks. Mutat Res 601:113-24
Doerr, Jeanette R; Malone, Cindy S; Fike, Francesca M et al. (2005) Patterned CpG methylation of silenced B cell gene promoters in classical Hodgkin lymphoma-derived and primary effusion lymphoma cell lines. J Mol Biol 350:631-40
Patrone, Lisa; Henson, Sarah E; Wall, Randolph et al. (2004) A conserved sequence upstream of the B29 (Ig beta, CD79b) gene interacts with YY1. Mol Biol Rep 31:1-11
Gordon, Melinda S; Kanegai, Cindy M; Doerr, Jeanette R et al. (2003) Somatic hypermutation of the B cell receptor genes B29 (Igbeta, CD79b) and mb1 (Igalpha, CD79a). Proc Natl Acad Sci U S A 100:4126-31
Patrone, Lisa; Henson, Sarah E; Teodorovic, Jelena et al. (2003) Gene expression patterns in AIDS versus non-AIDS-related diffuse large B-cell lymphoma. Exp Mol Pathol 74:129-39
French, Samuel W; Malone, Cindy S; Shen, Rhine R et al. (2003) Sp1 transactivation of the TCL1 oncogene. J Biol Chem 278:948-55
Hoyer, Katrina K; French, Samuel W; Turner, Devin E et al. (2002) Dysregulated TCL1 promotes multiple classes of mature B cell lymphoma. Proc Natl Acad Sci U S A 99:14392-7

Showing the most recent 10 out of 42 publications