Disease relevance of VPREB1

• By the use of a monoclonal anti VpreB antibody, preB cells were isolated from two adult bone marrow samples, and the VH repertoire was analyzed and compared to fetal, XLA (X-linked agammaglobulinemia), and adult B repertoires [1].
• VpreB RNA was also expressed in the neoplastic cells of one of three patients with acute undifferentiated leukemias [2].
• Northern blot analysis of RNAs from 63 leukemia samples showed that VpreB RNA was present in malignancies of precursor B cells, the expression being a feature of both common acute lymphoblastic leukemia (ALL) (CD10+) and null ALL (CD10-) [2].
• Chronic myeloid leukemia blast crises of the B-precursor-cell type expressed the VpreB gene while myeloid blast crises did not [2].
• We have produced human VpreB, SL, two Fdmu (VH-CH1), and the two corresponding Fab-like (Fdmu-SL) recombinant proteins in baculovirus [3].

High impact information on VPREB1

• B cell precursors transiently express a pre-B cell receptor complex consisting of a rearranged mu heavy chain, a surrogate light chain composed of lambda5/14.1 and VpreB, and the immunoglobulin (Ig)-associated signal transducing chains, Igalpha and Igbeta [4].
• However, some 20-40% of these B220(+)-CD19- cells also coexpress the NK1.1 surface molecule and do not express genes like VpreB or B29 restricted to the B cell lineage [5].
• It has been regarded as a tumor arising at the B, pre-B lymphocyte, or even stem cell level [6].
• Sequences encoding the entire putative second framework region and a stretch in the third framework region are identical in human and mouse VpreB. the human VpreB gene appears to be selectively expressed in human pre-B cell lines as an 0.85 kb poly(A)+ RNA [7].
• DNA from several mammals, including humans, was found to contain one or more restriction enzyme digested DNA fragments which hybridized to the mouse VpreB gene under stringencies demonstrating at least 70% nucleotide sequence homologies, indicating that the VpreB locus may be widespread and highly conserved among mammals [7].

Biological context of VPREB1

• The VpreB gene, encoding part of the surrogate light chain, the GGT2 gene and the BCRL4 pseudogene were also mapped within the lambda locus [8].
• These results strongly suggest that crosslinking of the micron-lambda 5-VpreB complex on the pre-B cell surface generates a signal that activates V kappa gene rearrangement, and that the lambda 5 and VpreB molecules are necessary for the spontaneous crosslinking of surface Ig on pre-B cells [9].
• Mice harboring a TSLP transgene had 5- to 700-fold fewer B and T precursors and no detectable pre-B lymphocyte colonyforming activity in the marrow or spleen [10].
• VpreB gene expression in hematopoietic malignancies: a lineage- and stage-restricted marker for B-cell precursor leukemias [2].
• Silencing of the surrogate light chain genes, VpreB and lambda5, then terminates preBCR expression to permit cell cycle exit, recombinase gene upregulation, and VJ(L) rearrangement by small pre-B cells destined to become B cells [11].

Anatomical context of VPREB1

• The chromosomal location of the human VpreB gene was determined by Southern blotting analysis of restriction enzyme-digested DNAs from a panel of 17 mouse-human somatic cell hybrids [12].
• The subpopulation of normal bone marrow cells bearing pre-B receptors included large and small pre-B cells exclusively, although pro-B cells also contained intracellular VpreB [13].
• After approximately 5 months in culture on BM stromal cells plus IL-7, BLIN-3 sublines emerged expressing mu heavy chain and VpreB on the cell surfaces (ie, pre-B-cell receptor [BCR](+)) [14].
• Flow cytometric analyses have shown that CD19- CD24+ CD45low lymphocytes express CD10, CD34, CD79a, CD179a (VpreB), and TdT markers, i.e., displayed antigenic properties of early B-cell progenitors [15].

Associations of VPREB1 with chemical compounds

• In a group of 145 women with different degrees of glucose tolerance, we compared IGI to the corresponding index with C-peptide, DeltaCP(30)/DeltaG(30), which better describes beta-cell function [16].

Other interactions of VPREB1

• A pre-BCR contains two immunoglobulin mu-heavy chains (muHC), two surrogate light chains (SLC) consisting of the non-covalently associated polypeptides, VpreB and lambda5, and the heterodimeric signaling transducer Igalpha/beta [17].
• Structure prediction revealed that these unique tails of VpreB and lambda5 protrude from the SLC at the position where the CDR3 of a conventional IgLchain would be located [17].
• The recombinant VpreB protein existed as a homodimer in solution [18].
• These data show that VpreB RNA expression is a marker of the malignant forms of precursor B cells, and that it appears at least as early as cytoplasmic CD22 and CD19 in tumors of the B-cell lineage [2].
• The VpreB gene, BCRL4, and gamma-glutamyl transpeptidase gene (GGT)-like sequences are also located within the lambda gene locus [19].

Analytical, diagnostic and therapeutic context of VPREB1

• By flow cytometry, biotinylated VpreB protein bound to surface Ig-positive B cells but not T cells [18].
• To analyze its interactions with Igs, we made recombinant human VpreB protein and measured its affinity for H and L chain V domains using surface plasmon resonance [18].
• A frequently used index of beta-cell function from the OGTT is the insulinogenic index, IGI [16].
• Thereafter, computed tomography data were imported to the Image-Guided Implantology system (IGI; DenX Advanced Dental Systems Ltd, Moshav Ora, Israel), and a precise 3-dimensional implant treatment plan was contemplated considering the compromised anatomy and the anticipated prosthesis [20].

References