Skip to main content
NCBI home page
Molecular and Cellular Biology logoLink to Molecular and Cellular Biology
. 1992 Mar;12(3):1126–1133. doi: 10.1128/mcb.12.3.1126

BLyF, a novel cell-type- and stage-specific regulator of the B-lymphocyte gene mb-1.

A L Feldhaus 1, D Mbangkollo 1, K L Arvin 1, C A Klug 1, H Singh 1
PMCID: PMC369544  PMID: 1545794

Abstract

The mb-1 gene encodes an integral membrane protein that appears to be required for the surface expression and signalling function(s) of the immunoglobulin receptor on B lymphocytes. The gene is expressed in a lineage-restricted manner. It is activated early in B-cell ontogeny, continues to be expressed in mature B cells, but is turned off in terminally differentiated plasma cells. We have identified the mb-1 promoter and functionally tested its activity by transient transfections. A 737-bp promoter fragment preferentially stimulates accurately initiated transcription in mb-1-expressing B cells. Deletion analysis of the promoter suggests the presence of two functional domains, proximal and distal. Both domains independently activate transcription from a heterologous promoter. The distal domain functions in a cell-type- and stage-specific manner, activating transcription in B cells but not in T cells or plasma cells. A 25-bp element within this domain is necessary and sufficient for activity. This element is recognized by a novel cell-type- and stage-specific transcription factor termed BLyF. The binding of BLyF completely correlates with the ability of the regulatory element to stimulate transcription. Thus, BLyF appears to positively regulate transcription of the mb-1 gene. Our results also suggest that the inactivity of the mb-1 locus in plasma cells is not simply due to the loss of BLyF activity.

Full text

PDF
1126

Images in this article

1128Image
on p.1128
1129Image
on p.1129
1129Image
on p.1129
1130Image
on p.1130
1131Image
on p.1131
1131Image
on p.1131

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Barberis A., Widenhorn K., Vitelli L., Busslinger M. A novel B-cell lineage-specific transcription factor present at early but not late stages of differentiation. Genes Dev. 1990 May;4(5):849–859. doi: 10.1101/gad.4.5.849. [DOI] [PubMed] [Google Scholar]
  2. Campbell K. S., Cambier J. C. B lymphocyte antigen receptors (mIg) are non-covalently associated with a disulfide linked, inducibly phosphorylated glycoprotein complex. EMBO J. 1990 Feb;9(2):441–448. doi: 10.1002/j.1460-2075.1990.tb08129.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Cherayil B. J., Pillai S. The omega/lambda 5 surrogate immunoglobulin light chain is expressed on the surface of transitional B lymphocytes in murine bone marrow. J Exp Med. 1991 Jan 1;173(1):111–116. doi: 10.1084/jem.173.1.111. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Grosschedl R., Baltimore D. Cell-type specificity of immunoglobulin gene expression is regulated by at least three DNA sequence elements. Cell. 1985 Jul;41(3):885–897. doi: 10.1016/s0092-8674(85)80069-6. [DOI] [PubMed] [Google Scholar]
  5. Hagman J., Travis A., Grosschedl R. A novel lineage-specific nuclear factor regulates mb-1 gene transcription at the early stages of B cell differentiation. EMBO J. 1991 Nov;10(11):3409–3417. doi: 10.1002/j.1460-2075.1991.tb04905.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Hermanson G. G., Eisenberg D., Kincade P. W., Wall R. B29: a member of the immunoglobulin gene superfamily exclusively expressed on beta-lineage cells. Proc Natl Acad Sci U S A. 1988 Sep;85(18):6890–6894. doi: 10.1073/pnas.85.18.6890. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Ho I. C., Bhat N. K., Gottschalk L. R., Lindsten T., Thompson C. B., Papas T. S., Leiden J. M. Sequence-specific binding of human Ets-1 to the T cell receptor alpha gene enhancer. Science. 1990 Nov 9;250(4982):814–818. doi: 10.1126/science.2237431. [DOI] [PubMed] [Google Scholar]
  8. Hombach J., Leclercq L., Radbruch A., Rajewsky K., Reth M. A novel 34-kd protein co-isolated with the IgM molecule in surface IgM-expressing cells. EMBO J. 1988 Nov;7(11):3451–3456. doi: 10.1002/j.1460-2075.1988.tb03219.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Hombach J., Tsubata T., Leclercq L., Stappert H., Reth M. Molecular components of the B-cell antigen receptor complex of the IgM class. Nature. 1990 Feb 22;343(6260):760–762. doi: 10.1038/343760a0. [DOI] [PubMed] [Google Scholar]
  10. Karasuyama H., Kudo A., Melchers F. The proteins encoded by the VpreB and lambda 5 pre-B cell-specific genes can associate with each other and with mu heavy chain. J Exp Med. 1990 Sep 1;172(3):969–972. doi: 10.1084/jem.172.3.969. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Kashiwamura S., Koyama T., Matsuo T., Steinmetz M., Kimoto M., Sakaguchi N. Structure of the murine mb-1 gene encoding a putative sIgM-associated molecule. J Immunol. 1990 Jul 1;145(1):337–343. [PubMed] [Google Scholar]
  12. Klemsz M. J., McKercher S. R., Celada A., Van Beveren C., Maki R. A. The macrophage and B cell-specific transcription factor PU.1 is related to the ets oncogene. Cell. 1990 Apr 6;61(1):113–124. doi: 10.1016/0092-8674(90)90219-5. [DOI] [PubMed] [Google Scholar]
  13. Kudo A., Melchers F. A second gene, VpreB in the lambda 5 locus of the mouse, which appears to be selectively expressed in pre-B lymphocytes. EMBO J. 1987 Aug;6(8):2267–2272. doi: 10.1002/j.1460-2075.1987.tb02500.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Lo K., Landau N. R., Smale S. T. LyF-1, a transcriptional regulator that interacts with a novel class of promoters for lymphocyte-specific genes. Mol Cell Biol. 1991 Oct;11(10):5229–5243. doi: 10.1128/mcb.11.10.5229. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Matsuo T., Kimoto M., Sakaguchi N. Direct identification of the putative surface IgM receptor-associated molecule encoded by murine B cell-specific mb-1 gene. J Immunol. 1991 Mar 1;146(5):1584–1590. [PubMed] [Google Scholar]
  16. Müller M. M., Ruppert S., Schaffner W., Matthias P. A cloned octamer transcription factor stimulates transcription from lymphoid-specific promoters in non-B cells. Nature. 1988 Dec 8;336(6199):544–551. doi: 10.1038/336544a0. [DOI] [PubMed] [Google Scholar]
  17. Nomura J., Matsuo T., Kubota E., Kimoto M., Sakaguchi N. Signal transmission through the B cell-specific MB-1 molecule at the pre-B cell stage. Int Immunol. 1991 Feb;3(2):117–126. doi: 10.1093/intimm/3.2.117. [DOI] [PubMed] [Google Scholar]
  18. Reth M., Hombach J., Wienands J., Campbell K. S., Chien N., Justement L. B., Cambier J. C. The B-cell antigen receptor complex. Immunol Today. 1991 Jun;12(6):196–201. doi: 10.1016/0167-5699(91)90053-V. [DOI] [PubMed] [Google Scholar]
  19. Sakaguchi N., Kashiwamura S., Kimoto M., Thalmann P., Melchers F. B lymphocyte lineage-restricted expression of mb-1, a gene with CD3-like structural properties. EMBO J. 1988 Nov;7(11):3457–3464. doi: 10.1002/j.1460-2075.1988.tb03220.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Sakaguchi N., Melchers F. Lambda 5, a new light-chain-related locus selectively expressed in pre-B lymphocytes. Nature. 1986 Dec 11;324(6097):579–582. doi: 10.1038/324579a0. [DOI] [PubMed] [Google Scholar]
  21. Singh H., LeBowitz J. H., Baldwin A. S., Jr, Sharp P. A. Molecular cloning of an enhancer binding protein: isolation by screening of an expression library with a recognition site DNA. Cell. 1988 Feb 12;52(3):415–423. doi: 10.1016/s0092-8674(88)80034-5. [DOI] [PubMed] [Google Scholar]
  22. Singh H., Sen R., Baltimore D., Sharp P. A. A nuclear factor that binds to a conserved sequence motif in transcriptional control elements of immunoglobulin genes. Nature. 1986 Jan 9;319(6049):154–158. doi: 10.1038/319154a0. [DOI] [PubMed] [Google Scholar]
  23. Travis A., Hagman J., Grosschedl R. Heterogeneously initiated transcription from the pre-B- and B-cell-specific mb-1 promoter: analysis of the requirement for upstream factor-binding sites and initiation site sequences. Mol Cell Biol. 1991 Nov;11(11):5756–5766. doi: 10.1128/mcb.11.11.5756. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Tsubata T., Reth M. The products of pre-B cell-specific genes (lambda 5 and VpreB) and the immunoglobulin mu chain form a complex that is transported onto the cell surface. J Exp Med. 1990 Sep 1;172(3):973–976. doi: 10.1084/jem.172.3.973. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Venkitaraman A. R., Williams G. T., Dariavach P., Neuberger M. S. The B-cell antigen receptor of the five immunoglobulin classes. Nature. 1991 Aug 29;352(6338):777–781. doi: 10.1038/352777a0. [DOI] [PubMed] [Google Scholar]
  26. Westin G., Gerster T., Müller M. M., Schaffner G., Schaffner W. OVEC, a versatile system to study transcription in mammalian cells and cell-free extracts. Nucleic Acids Res. 1987 Sep 11;15(17):6787–6798. doi: 10.1093/nar/15.17.6787. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Molecular and Cellular Biology are provided here courtesy of Taylor & Francis

RESOURCES