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Gene Review

Vpreb2  -  pre-B lymphocyte gene 2

Mus musculus

Synonyms: CD179b, Immunoglobulin omega chain, Protein VPreB2, VpreB1, Vpreb-2
 
 
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Disease relevance of Vpreb2

 

High impact information on Vpreb2

  • Hence, B-lineage commitment is determined neither by immunoglobulin DJ rearrangement nor by the expression of E2A, EBF, lambda5, VpreB, Igalpha and Igbeta [2].
  • VpreB1(-/-) VpreB2(-/-) mice were impaired in their B cell development at the transition from pre-BI to large pre-BII cells [3].
  • We find that expression of terminal deoxynucleotidyl transferase (TdT), lambda 5, and VpreB is predominantly restricted to the Pro-B stages [4].
  • We have investigated whether the pre-BCR also signals downregulation of the SLC genes (VpreB and lambda5), thereby limiting this expansion [5].
  • A VpreB1-promoter-driven transgene shows the same pattern, therefore suggesting that VpreB1 is similarly regulated and thereby defines the promoter as a target for transcriptional silencing [5].
 

Biological context of Vpreb2

  • The 3' end of VpreB encoding the 26 carboxyl terminal amino acids shows no homology to any known nucleotide sequence [6].
  • The other gene, called VpreB2, which has not yet been located within the genome, shows 97% nucleotide sequence homology to VpreB1 in an area of 1 kb which covers the coding region of the gene.(ABSTRACT TRUNCATED AT 250 WORDS)[6]
  • Identification of a tissue- and differentiation stage-specific enhancer of the VpreB1 gene [7].
  • To find a promoter and other potential cis-acting regulatory elements, a 700-bp fragment 5' of the transcription start sites of the VpreB1 gene was used in gene transfer experiments and found to act as a promoter in pre-B lymphocytes [8].
  • VpreB1 and VpreB2 were co-expressed in the fetal liver of CB17 mice, where peak expression of each gene occurred at days 16-17 of gestation [9].
 

Anatomical context of Vpreb2

 

Associations of Vpreb2 with chemical compounds

  • It therefore appears that, at least in transformed cell lines, the expression of VpreB and lambda 5 is not directly regulated by the expression of microH, kappa L, or lambda L chains, LPS reactivity, or the Ly1 surface antigen [1].
  • Herein, we show that the molecules, lambda5 and VpreB, which comprise the surrogate light chain component of the pre-B cell receptor, are reduced in pro-B/early pre-B cells derived in vitro from the bone marrow of 18-27 months old BALB/c mice after stimulation with IL-7 [11].
 

Physical interactions of Vpreb2

  • A complex of glycoproteins is associated with VpreB/lambda 5 surrogate light chain on the surface of mu heavy chain-negative early precursor B cell lines [12].
  • Gene transfer and gel-shift assays demonstrate that EBB-1 is identical to Pax-5 and binds to promoters of VpreB and lambda5 as well as the KI and KII sites [13].
 

Regulatory relationships of Vpreb2

  • Pre-B lymphocyte-specific transcriptional control of the mouse VpreB gene [8].
  • The lambda 5 protein is expressed in pre-B cells in association with VpreB and mu-heavy chains, and is critical for differentiation to the B cell stage [14].
 

Other interactions of Vpreb2

  • This would suggest that one of either lambda 5 or VpreB can make a pre-BCR-like complex which is still able to signal allelic exclusion but not proliferation [15].
  • The deduced amino acid sequence of the 8HS-20 cDNA displayed homology to a B cell specific gene, VpreB-1, and to members of the immunoglobulin supergene family including V lambda, V kappa, VH, TCRV alpha, V beta and CD8 [16].
  • A pre-B- and B cell-specific DNA-binding protein, EBB-1, which binds to the promoter of the VpreB1 gene [17].
  • During B-lymphocyte development in mouse fetal liver and bone marrow, a pre-B I cell stage is reached in which the cells express B-lineage-specific genes, such as CD19, Ig alpha and Igbeta and VpreB and lambda5, which encode the surrogate light (SL) chain [18].
  • These BM cells express lambda5 and VpreB but not terminal deoxytransferase (TdT) and Bcl-2, and approximately 50 % of them are in cell cycle [19].
 

Analytical, diagnostic and therapeutic context of Vpreb2

  • Monoclonal antibodies specific for the pre-B cell receptor, i. e. for VpreB, lambda5, or muH chains, do not perturb B cell development in these organ cultures up to and including the CD25+ small pre-BII cell stage [20].

References

  1. The expression of the mouse VpreB/lambda 5 locus in transformed cell lines and tumors of the B lineage differentiation pathway. Kudo, A., Thalmann, P., Sakaguchi, N., Davidson, W.F., Pierce, J.H., Kearney, J.F., Reth, M., Rolink, A., Melchers, F. Int. Immunol. (1992) [Pubmed]
  2. Long-term in vivo reconstitution of T-cell development by Pax5-deficient B-cell progenitors. Rolink, A.G., Nutt, S.L., Melchers, F., Busslinger, M. Nature (1999) [Pubmed]
  3. Loss of precursor B cell expansion but not allelic exclusion in VpreB1/VpreB2 double-deficient mice. Mundt, C., Licence, S., Shimizu, T., Melchers, F., Mårtensson, I.L. J. Exp. Med. (2001) [Pubmed]
  4. The regulated expression of B lineage associated genes during B cell differentiation in bone marrow and fetal liver. Li, Y.S., Hayakawa, K., Hardy, R.R. J. Exp. Med. (1993) [Pubmed]
  5. The pre-B-cell receptor induces silencing of VpreB and lambda5 transcription. Parker, M.J., Licence, S., Erlandsson, L., Galler, G.R., Chakalova, L., Osborne, C.S., Morgan, G., Fraser, P., Jumaa, H., Winkler, T.H., Skok, J., Mårtensson, I.L. EMBO J. (2005) [Pubmed]
  6. A second gene, VpreB in the lambda 5 locus of the mouse, which appears to be selectively expressed in pre-B lymphocytes. Kudo, A., Melchers, F. EMBO J. (1987) [Pubmed]
  7. Identification of a tissue- and differentiation stage-specific enhancer of the VpreB1 gene. Persson, C., Mårtensson, A., Mårtensson, I.L. Eur. J. Immunol. (1998) [Pubmed]
  8. Pre-B lymphocyte-specific transcriptional control of the mouse VpreB gene. Okabe, T., Bauer, S.R., Kudo, A. Eur. J. Immunol. (1992) [Pubmed]
  9. The murine VpreB1 and VpreB2 genes both encode a protein of the surrogate light chain and are co-expressed during B cell development. Dul, J.L., Argon, Y., Winkler, T., ten Boekel, E., Melchers, F., Mårtensson, I.L. Eur. J. Immunol. (1996) [Pubmed]
  10. The proteins encoded by the VpreB and lambda 5 pre-B cell-specific genes can associate with each other and with mu heavy chain. Karasuyama, H., Kudo, A., Melchers, F. J. Exp. Med. (1990) [Pubmed]
  11. The reduced expression of surrogate light chains in B cell precursors from senescent BALB/c mice is associated with decreased E2A proteins. Sherwood, E.M., Xu, W., King, A.M., Blomberg, B.B., Riley, R.L. Mech. Ageing Dev. (2000) [Pubmed]
  12. A complex of glycoproteins is associated with VpreB/lambda 5 surrogate light chain on the surface of mu heavy chain-negative early precursor B cell lines. Karasuyama, H., Rolink, A., Melchers, F. J. Exp. Med. (1993) [Pubmed]
  13. Pax-5 is identical to EBB-1/KLP and binds to the VpreB and lambda5 promoters as well as the KI and KII sites upstream of the Jkappa genes. Tian, J., Okabe, T., Miyazaki, T., Takeshita, S., Kudo, A. Eur. J. Immunol. (1997) [Pubmed]
  14. Identification and localization of a developmental stage-specific promoter activity from the murine lambda 5 gene. Yang, J., Glozak, M.A., Blomberg, B.B. J. Immunol. (1995) [Pubmed]
  15. VpreB1/VpreB2/lambda 5 triple-deficient mice show impaired B cell development but functional allelic exclusion of the IgH locus. Shimizu, T., Mundt, C., Licence, S., Melchers, F., Mårtensson, I.L. J. Immunol. (2002) [Pubmed]
  16. A novel gene product associated with mu chains in immature B cells. Shirasawa, T., Ohnishi, K., Hagiwara, S., Shigemoto, K., Takebe, Y., Rajewsky, K., Takemori, T. EMBO J. (1993) [Pubmed]
  17. A pre-B- and B cell-specific DNA-binding protein, EBB-1, which binds to the promoter of the VpreB1 gene. Okabe, T., Watanabe, T., Kudo, A. Eur. J. Immunol. (1992) [Pubmed]
  18. Fidelity and infidelity in commitment to B-lymphocyte lineage development. Rolink, A.G., Schaniel, C., Busslinger, M., Nutt, S.L., Melchers, F. Immunol. Rev. (2000) [Pubmed]
  19. GL7 defines the cycling stage of pre-B cells in murine bone marrow. Murasawa, M., Okada, S., Obata, S., Hatano, M., Moriya, H., Tokuhisa, T. Eur. J. Immunol. (2002) [Pubmed]
  20. The B cell receptor, but not the pre-B cell receptor, mediates arrest of B cell differentiation. Ceredig, R., Rolink, A.G., Melchers, F., Andersson, J. Eur. J. Immunol. (2000) [Pubmed]
 
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