Disease relevance of Vpreb2

• Fusion of plasmacytoma cells with normal pre B cells to generate pre B hybridomas leads to down-regulation of VpreB/lambda 5 expression.(ABSTRACT TRUNCATED AT 250 WORDS)[1]

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

• A second gene, VpreB in the lambda 5 locus of the mouse, which appears to be selectively expressed in pre-B lymphocytes [6].
• Southern blot analysis of DNA from liver (germ line) and 70Z/3 pre-B cell lines reveals two genes which hybridize to the VpreB gene [6].
• Finally, single-cell reverse transcriptase-polymerase chain reaction on such sorted bone marrow cells detected VpreB1 and VpreB2 expression in at least 30% of all pro-B/pre-BI cells and large Ig heavy chain, surrogate light chain (pre-B receptor) expressing pre-BII cells [9].
• Using transfected COS cells expressing either VpreB1 or VpreB2, a PCR assay was developed to examine the steady state level of transcripts from each gene [9].
• The murine pre-B cell-specific genes VpreB and lambda 5, as well as the murine gene for mu heavy chain, were introduced into Ltk- fibroblast cells which normally do not express these genes [10].

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