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, signaling 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.

Patrone L, Henson SE, Teodorovic J, Malone CS, French SW, Wall R, Teitell MA   Gene expression patterns in AIDS versus non-AIDS-related diffuse large B-cell lymphomaExp Mol Pathol, 2003; 74(2): 129-39.

Gordon MS, Kanegai CM, Doerr JR, Wall R   Somatic hypermutation of the B cell receptor genes B29 (Igbeta, CD79b) and mb1 (Igalpha, CD79a) Proc Natl Acad Sci U S A, 2003; 100(7): 4126-31.

French SW, Malone CS, Shen RR, Renard M, Henson SE, Miner MD, Wall R, Teitell MA   Sp1 transactivation of the TCL1 oncogene The Journal of biological chemistry. , 2003; 278(2): 948-55.

Hoyer KK, French SW, Turner DE, Nguyen MT, Renard M, Malone CS, Knoetig S, Qi CF, Su TT, Cheroutre H, Wall R, Rawlings DJ, Morse HC, Teitell MA   Dysregulated TCL1 promotes multiple classes of mature B cell lymphoma Proceedings of the National Academy of Sciences of the United States of America. , 2002; 99(22): 14392-7.

Malone CS and Wall R   Bob1 (OCA-B/OBF-1) differential transactivation of the B cell-specific TATA-less B29 (Ig-beta) and mb-1 (Ig-alpha) gene promoters, Journal of Immunology, 2002; 168: 3369-3375.

French SW, Dawson DW, Miner MD, Doerr JR, Malone CS, Wall R, Teitell MA   DNA methylation profiling: a new tool for evaluating hematologic malignancies Clinical immunology (Orlando, Fla.) , 2002; 103(3 Pt 1): 217-30.

Patrone L, Damore MA, Lee MB, Malone CS, Wall R   Genes expressed during the IFN gamma-induced maturation of pre-B cells Molecular immunology. , 2002; 38(8): 597-606.

Malone CS, Miner MD, Doerr JR, Jackson JP, Jacobsen SE, Wall R, Teitell M  CmC(A/T)GG DNA methylation in mature B cell lymphoma gene silencingProceedings of the National Academy of Sciences of the United States of America. , 2001; 98(18): 10404-9.

Malone CS, Omori SA, Gangadharan D, Wall R   Leukocyte-specific expression of the pp52 (LSP1) promoter is controlled by the cis-acting pp52 silencer and anti-silencer elements Gene. , 2001; 268(1-2): 9-16.

Miyoshi EK, Stewart PL, Kincade PW, Lee MB, Thompson AA, Wall R   Aberrant expression and localization of the cytoskeleton-binding pp52 (LSP1) protein in hairy cell leukemia Leukemia research. , 2001; 25(1): 57-67.

Gordon MS, Kato RM, Lansigan F, Thompson AA, Wall R, Rawlings DJ   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, 2000; 97 (10): 5504-5509.

Malone CS, Patrone L, Wall R   An essential octamer motif in the mb-1 (Ig-alpha) promoter, Molecular Immunology, 2000; 37: 321-328.

Malone CS, Patrone L, Buchanan KL, Webb CF, Wall R   An upstream Oct-1- and Oct-2-binding silencer governs B29 (Ig beta) gene expression Journal of immunology (Baltimore, Md. : 1950) , 2000; 164(5): 2550-6.

Teitell M, Damore MA, Sulur GG, Turner DE, Stern MH, Said JW, Denny CT, Wall R  TCL1 oncogene expression in AIDS-related lymphomas and lymphoid tissuesProceedings of the National Academy of Sciences of the United States of America. , 1999; 96(17): 9809-14.

Thompson AA, Do HN, Saxon A, Wall R   Widespread B29 (CD79b) gene defects and loss of expression in chronic lymphocytic leukemia Leukemia & lymphoma. , 1999; 32(5-6): 561-9.

Thompson AA, Talley JA, Do NH, Kagan HL, Kunkel L, Berenson J, Cooper MD, Saxon A and Wall R   Aberrations of the B cell receptor B29 (CD79b) gene in chronic lymphocytic leukemia, Blood, 1997; 90: 1387-1394.

Omori SA, Smale S, O’Shea-Greenfield A and Wall R   Differential interaction of nuclear factors with the leukocyte-specific pp52 promoter in B and T cells, J. Immunol, 1997; 159: 1800-1808.

Malone CS, Omori SA and Wall R   Silencer elements controlling the B29 (IgB) promoter are neither promoter- nor cell-type specific, Proc. Nat. Acad. Sci. USA, 1997; 94: 12314-12319.

Gilly M, Damore MA, Wall R   A promoter ISRE and dual 5′ YY1 motifs control IFN-gamma induction of the IRG-47 G-protein gene Gene. , 1996; 179(2): 237-44.

Damore MA, Omori SA, Wall R   INF-gamma induces the Kappa intron enhancer via an IFN-stimulated response element, Journal of Immunology, 1996; 156: 2451-2457.

Thompson AA, Omori SA, Gilly MJ, May W, Gordon MS, Wood WJ, Miyoshi E, Malone CS, Gimble J, Denny CT, Wall R   Alternatively spliced exons encode the tissue-specific 5′ termini of leukocyte pp52 and stromal cell S37 mRNA isoforms Genomics. , 1996; 32(3): 352-7.

Thompson AA, Wood WJ, Gilly MJ, Damore MA, Omori SA, Wall R   The promoter and 5′ flanking sequences controlling human B29 gene expression Blood. , 1996; 87(2): 666-73.

Fasel NJ, Deglon N, Beghdadi-Rais C, Law R, Bron C, Wall R   Minimal membrane and secreted mu poly(A) signals specify developmentally-regulated immunoglobulin heavy chain mRNA ratios without RNA splicing Molecular immunology. , 1994; 31(7): 563-6.

Omori SA, Wall R   Multiple motifs regulate the B-cell-specific promoter of the B29 gene Proceedings of the National Academy of Sciences of the United States of America. , 1993; 90(24): 11723-7.