The goal of this grant and its predecessor is to study the molecular events related to heave chain gene expression. The last grant focused on the structure and rearrangement of C/H genes. An in depth characterization of the Mu-C delta locus in mouse and man has provided a framework to address fundamental issues of transcriptional and post-transcriptional regulation. In this renewal, we propose to extend the work on Mu-delta regulation, primarily be exploiting in vitro expression technology, with an eye toward understanding the differential roles of the gene products. Specifically, we will determine the levels at which IgM and IgD are regulated in human B cells; significance draws on the dramatic evolutionary divergence of C delta structure in this species while retaining phenotypic conservation in IgD function. We propose a series of transfection studies aimed at fine dissection of 3' and regulation in the murine mu-delta locus. That is, what is the mechanism(s) governing membrane vs. secreted carboxyl-terminus and/or Mu vs delta exon selection? We propose studies on V/H promoter-associated sequences, focusing on protein: DNA interactions and the regulatory effects of T cells on this interaction. We propose a novel cDNA cloning strategy for characterizing putative transcription termination and promoter-associated factors. We provide preliminary feasibility data and design projects for exploitation of antigen-specific IgM and IgD transfected B cell lines. Specifically, we will investigate the role of phosphorylcholine-specific mIg receptors, both in wild- type and structurally modified forms, in B cell activation, processing, and antigen presentation. Finally, we devise a molecular approach to address the differential roles of mIgM and IgD in neonatal B cell tolerance.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI018016-10
Application #
3127636
Study Section
Allergy and Immunology Study Section (ALY)
Project Start
1980-09-01
Project End
1992-08-31
Budget Start
1989-09-01
Budget End
1990-08-31
Support Year
10
Fiscal Year
1989
Total Cost
Indirect Cost
Name
University of Texas Sw Medical Center Dallas
Department
Type
Overall Medical
DUNS #
City
Dallas
State
TX
Country
United States
Zip Code
75390
Wang, Bin; Lin, Danjuan; Li, Chuan et al. (2003) Multiple domains define the expression and regulatory properties of Foxp1 forkhead transcriptional repressors. J Biol Chem 278:24259-68
Emili, Andrew; Shales, Michael; McCracken, Susan et al. (2002) Splicing and transcription-associated proteins PSF and p54nrb/nonO bind to the RNA polymerase II CTD. RNA 8:1102-11
Satterwhite, E; Sonoki, T; Willis, T G et al. (2001) The BCL11 gene family: involvement of BCL11A in lymphoid malignancies. Blood 98:3413-20
Mathur, M; Tucker, P W; Samuels, H H (2001) PSF is a novel corepressor that mediates its effect through Sin3A and the DNA binding domain of nuclear hormone receptors. Mol Cell Biol 21:2298-311
Kaplan, M H; Zong, R T; Herrscher, R F et al. (2001) Transcriptional activation by a matrix associating region-binding protein. contextual requirements for the function of bright. J Biol Chem 276:21325-30
Kenny, J J; Derby, E G; Yoder, J A et al. (2000) Positive and negative selection of antigen-specific B cells in transgenic mice expressing variant forms of the V(H)1 (T15) heavy chain. Int Immunol 12:873-85
Herrscher, R F; Kaplan, M H; Lelsz, D L et al. (1995) The immunoglobulin heavy-chain matrix-associating regions are bound by Bright: a B cell-specific trans-activator that describes a new DNA-binding protein family. Genes Dev 9:3067-82
Kenny, J J; Stall, A M; Fisher, R T et al. (1995) Ig gamma 2b transgenes promote B cell development but alternate developmental pathways appear to function in different transgenic lines. J Immunol 154:5694-705
Liu, K J; Parikh, V S; Tucker, P W et al. (1994) Surface immunoglobulins mediate efficient transport of antigen to lysosomal compartments resulting in enhanced specific antigen presentation by B cells. Eur J Immunol 24:2755-60
Michnoff, C H; Parikh, V S; Lelsz, D L et al. (1994) Mutations within the NH2-terminal transmembrane domain of membrane immunoglobulin (Ig) M alters Ig alpha and Ig beta association and signal transduction. J Biol Chem 269:24237-44

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