Cancer Institute A national cancer institute
designated cancer center

Dean W. Felsher

Publication Details

  • A NOVEL OCTAMER REGULATORY ELEMENT IN THE V(H)11 LEADER EXON OF B-1 CELLS JOURNAL OF IMMUNOLOGY Goodglick, L., Felsher, D. W., Neshat, M. S., Braun, J. 1995; 154 (9): 4546-4556

    Abstract:

    B-1 cells (CD5 B cells) represent an initial fetal wave of B cell lymphopoiesis. B-1 cells have fundamental properties that are unique from conventional B cells, including a restricted Ab repertoire. We investigated the mechanism for the overrepresentation of one such Ig H chain variable-region gene, VH11, by murine B-1 cells. We postulated that a cis-regulatory element contributed to the use of VH11. We observed that the DNA encoding the leader peptide of VH11 was atypically A/T rich and thus was a candidate for nuclear protein binding. By electrophoretic mobility shift analysis, we found that the VH11 leader DNA specifically bound to three protein complexes present in the nucleus of the B-1 cell line AJ9. Of these bands, one was ubiquitous for all cells examined (lymphoid and nonlymphoid); another band was present only in B cells, and the third band was specific for B-1 cells that expressed VH11 or VH12. In addition to its binding properties, the VH11 leader sequence also displayed modest tissue-specific enhancer activity. By DNA footprint analysis, all three protein complexes were found to bind to an octamer motif embedded within the VH11 leader DNA. To identify the octamer-binding proteins, a panel of octamer-specific Abs was used. We found that the ubiquitous band was Oct-1, and the B cell-specific band was Oct-2. The B-1 cell-specific nuclear binding protein was neither Oct-1 nor Oct-2, but may be a novel POU domain protein. We hypothesize that the VH11 leader octamer site may target this gene for preferential rearrangement and/or expression and therefore would be a contributing factor in the increased use of this gene by B-1 cells.

    View details for Web of Science ID A1995QU82500033

    View details for PubMedID 7722308

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