The pre-B-cell receptor (pre-BCR) is composed of two immunoglobulin mu heavy chains and two surrogate light chains, which associate with the signaling molecules Igalpha and Igbeta (Igalpha/beta). The production of a functional pre-BCR is the first checkpoint in the current model of B-cell development. The pre-BCR mediates signals resulting in heavy chain allelic exclusion, down-regulation of the recombination machinery, developmental progression, V(H) repertoire selection, proliferation and down-regulation of the surrogate light chain genes. Recent studies suggest that some of these processes could take place at an earlier stage in B-cell development than previously thought, and might not result from signals mediated by the pre-BCR.
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http://dx.doi.org/10.1016/j.coi.2007.02.006 | DOI Listing |
Cell Mol Life Sci
November 2024
Laboratory of Molecular Immunology and Immunotherapy, Blood Research Institute, Versiti, Milwaukee, WI, USA.
IQGAP1 is a multi-functional scaffold protein. However, its role in B cell development and function is unknown. Here, we show IQGAP1 as an essential scaffold that regulates early B cell development and function.
View Article and Find Full Text PDFPLoS One
September 2024
Monash Biomedicine Discovery Institute, and Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC, Australia.
Nat Immunol
September 2024
Research Institute of Molecular Pathology, Vienna BioCenter, Vienna, Austria.
Early B cell lymphopoiesis depends on E2A, Ebf1, Pax5 and Ikaros family members. In the present study, we used acute protein degradation in mice to identify direct target genes of these transcription factors in pro-B, small pre-B and immature B cells. E2A, Ebf1 and Pax5 predominantly function as transcriptional activators by inducing open chromatin at their target genes, have largely unique functions and are essential for early B cell maintenance.
View Article and Find Full Text PDFEMBO Mol Med
September 2024
University of Cambridge, Cancer Research UK Cambridge Institute, Robinson Way, Cambridge, CB2 0RE, UK.
We have developed and validated a highly specific, versatile antibody to the extracellular domain of human LGR5 (α-LGR5). α-LGR5 detects LGR5 overexpression in >90% of colorectal cancer (CRC), hepatocellular carcinoma (HCC) and pre-B-ALL tumour cells and was used to generate an Antibody-Drug Conjugate (α-LGR5-ADC), Bispecific T-cell Engager (α-LGR5-BiTE) and Chimeric Antigen Receptor (α-LGR5-CAR). α-LGR5-ADC was the most effective modality for targeting LGR5 cancer cells in vitro and demonstrated potent anti-tumour efficacy in a murine model of human NALM6 pre-B-ALL driving tumour attrition to less than 1% of control treatment.
View Article and Find Full Text PDFInt J Mol Sci
July 2024
Institute of Immunology, Ulm University Medical Center, 89081 Ulm, Germany.
Philadelphia-chromosome-positive acute lymphoblastic leukemia (Ph ALL) is characterized by reciprocal chromosomal translocation between chromosome 9 and 22, leading to the expression of constitutively active oncogenic BCR-ABL1 fusion protein. CXC chemokine receptor 4 (CXCR4) is essential for the survival of BCR-ABL1-transformed mouse pre-B cells, as the deletion of CXCR4 induces death in these cells. To investigate whether CXCR4 inhibition also effectively blocks BCR-ABL1-transformed cell growth in vitro, in this study, we explored an array of peptide-based inhibitors of CXCR4.
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