Genes and Mechanisms Controlling B Lymphocyte Development
The stages in B lymphocyte development are delineated by the activation and transcription of immunoglobulin genes and other tissue-specific genes. Research in the Wall lab is directed at discovering the molecular mechanisms which control B cell development by the cloning of B-cell-specific genes and the characterization of their function and regulation. The best studied B-cell-specific gene identified here (B29) codes for a critical member of the antigen receptor complex on B cells and is essential for B cell activation and development. Transcription factors shown to control the B29 promoter are now known to regulate the appearance of the earliest committed lymphoid precursor cells. B29 expression is critical for development of the earliest B lineage precursors (i.e. proB è pre B cells). Aberrant expression of the B29 gene is implicated in human chronic lymphocytic leukemia (B-CLL). Another area of active research in this Lab is directed at resolving the cytokines, signalling events and transcription factors which activate and control immunoglobulin gene expression in B-cell development. This research uses the combined approaches of molecular biology, immunology and genetics.
Miyoshi, E.K., Stewart, P.L., Kincade, P.W., Lee, M.B., Thompson, A.A., Wall, R. (2001) Aberrant expression and localization of the cytoskeleton-binding protein pp52 (LSP1) protein in hairy cell leukemia. Leukemia Research 25 (1): 57-67.
Malone, CS, Omori, SA, Gangadharan, D, and Wall, R (2001) Leukocyte-specific expression of the pp52 (LSP1) promoter is controlled by the cis-acting pp52 silencer and anti-silencer elements. Gene 268: 9-16.
Malone, CS, Miner, M, Doerr, JR, Jackson, JP, Jacobsen, SE, Wall, R, and Teitell, M (2001) CC(A/T)GG DNA Methylation in Mature B Cell Lymphoma Silencing. Proceedings of the National Academy of Sciences, USA Aug. 28, vol.98, issue 18:.
Malone, C.S., Patrone, L., Wall, R. (2000) An essential octamer motif in the mb-1 (Ig-alpha) promoter. Molecular Immunology 37: 321-328.
Gordon, MS, Kato, RM, Lansigan, F, Thompson, AA, Wall, R, Rawlings, DJ (2000) Aberrant B cell receptor signalling from B29 (Ig-beta, CD79b) gene mutations of chronic lymphocytic leukemia B cells. Proceedings of the National Academy of Sciences 97 (10): 5504-5509.
Malone, CS, Patrone, L, Buchanan, KL, Webb, CF, Wall, R (2000) An upstream Oct-1 and Oct-2-binding silencer governs B29 (Ig-beta) gene expression. Journal of Immunology 164: 2550-2556.
Teitell, MA, Damore, MA, Sulur, GG, Turner, DE, Stern, M-H, Said, JW, Denny, CT, Wall, R. (1999) TCL1 oncogene expression in AIDS-related lymphomas and lymphoid tissues. Proceedings of the National Academy of Sciences 96: 9809-9814.
Thompson, AA, Do, HN, Saxon, A, Wall, R. (1999) Widespread B29 (CD79b) gene defects and loss of expression in chronic lymphocytic leukemia. Leukemia and Lymphoma 32 (5-6): 561-569.
Malone, C.S., Omori, S. A., and Wall, R. (1997) Silencer elements controlling the B29 (IgB) promoter are neither promoter- nor cell-type specific. Proc. Nat. Acad. Sci. USA 94: 12314-12319.
Omori, S. A., Smale, S., O'Shea-Greenfield, A., and Wall, R. (1997) Differential interaction of nuclear factors with the leukocyte-specific pp52 promoter in B and T cells. J. Immunol. 159: 1800-1808.
Thompson, A. A., Talley, J. A., Do, N. H., Kagan, H. L., Kunkel, L., Berenson, J., Cooper, M.D., Saxon, A., and Wall, R. (1997) Aberrations of the B cell receptor B29 (CD79b) gene in chronic lymphocytic leukemia. Blood 90: 1387-1394.
AA Thompson, SA Omori, MJ Gilly, W May, MS Gordon, WJ Wood Jr, EK Miyoshi, CS Malone, J Gimble, CJ Denny, R Wall (1996) Alternatively spliced exons encode the tissue-specific 5' termini of leukocyte pp52 and stromal cell S37 mRNA isoforms. Genomics 32: 352-357.
AA Thompson, WJ Wood Jr, MJ Gilly, MA Damore, SA Omori, R Wall (1996) The promoter and 5' flanking sequences controlling human B29 gene expression. Blood 87 (2): 666-673.
Damore, MA, Omori, SA, Wall, R. (1996) INF-gamma induces the Kappa intron enhancer via an IFN-stimulated response element. Journal of Immunology 156: 2451-2457.
Gilly, M, Damore, MA, Wall, R. (1996) A promoter ISRE and dual 5' YY1 motifs control IFN-gamma induction of the IRG-47 G-protein gene. Gene 179: 237-244.
NJ Fasel, N Deglon, C Beghdadi-Rais, R Law, C Bron, R Wall (1994) Minimal membrane and secreted Mu poly(A) signals specify developmentally-regulated immunoglobulin heavy chain mRNA ratios without RNA splicing. Molecular Immunology 31(7): 563-566.
SA Omori, R Wall (1993) Multiple
Motifs regulate the B-cell-specific promoter of the B29 gene. Proc. Natl Acad
of SCI USA 90: 11723-11727.
Randolph Wall's Support