Project description:The B cell antigen receptor (BCR) is a signaling complex that mediates differentiation stage-specific cell fate decisions in B lymphocytes. While several studies have evidenced differences in signal transduction components as being key to contrasting phenotypic outcomes, little is known about the differential BCR-triggered gene transcription. Here we defined transcriptional changes underlying BCR-induced apoptosis and proliferation of immature and mature B cells, respectively. These findings provide the first insights into the early transcriptional events leading to deletion or clonal expansion of B cells upon antigen recognition. Keywords: cell type comparison, development or differentiation design, time course, compound treatment design, microarray experiment record Total RNA was extracted from immature (IM) and mature (M) B cells both freshly isolated (0h) and stimulated with (BCR) or without (ctrl) anti-μ F(ab’)2 for 2, 8 or 24h. Following RNA extraction, one round of mRNA amplification was applied using the MessageAmpTM Kit (Ambion). All samples, including the amplified Universal Mouse Reference RNA (Stratagene) which served as a reference at each hybridization, were reverse-transcribed and indirectly labeled with Cy3 and Cy5 (Amersham). Quality was controlled by performing 6 or 8 hybridizations of each sample to the cDNA arrays using a dye-swap strategy. 94 arrays were used for hybridization in total.

2008-12-14 | E-GEOD-9215 | biostudies-arrayexpress

Gene inductions in response to BCR-crosslinking in TAK1-deficient B cell

Project description:BCR-induced gene expression profile in wild-type and B cell-specific TAK1-deficient B cells; to elucidate how TAK1 regulates BCR-mediated proliferative response Keywords: ordered

2005-08-11 | GSE3065 | GEO

Transcription profiling of mouse B cells expressing anti-HEL IgM BCR and IgMG BCR to investigate the effect of IgG cytoplasmic tail on BCR-respose genes

Project description:IgG cytoplasmic tail interferes with the induction of antigen-response genes Experiment Overall Design: Comparing antigen-induced genes between B cells expressing anti-HEL IgM BCR and IgMG BCR (chimeric receptor where the extracellular spacer, transmembrane, and cytoplasmic domain of IgM are replaced with those of IgG1)

2008-06-15 | E-GEOD-7218 | biostudies-arrayexpress

CD49d governs immune synapse formation through actin rearrangements and synchronizes BCR signaling in CLL

Project description:B cell receptor (BCR) signaling is a key determinant of chronic lymphocytic leukemia (CLL) pathophysiology. CD49d, the alpha4 subunit of the very late antigen-4 (VLA-4) integrin, can be activated by BCR signals; however, its role in modulating BCR functionality remains unknown. We used mouse models and primary human CLL to address this aspect. We found CD49d being not only required for bone marrow infiltration in TCL1 transgenic mice but also shaping human bone marrow infiltration patterns, along with patient outcome. In mice transplanted with TCL1 transgenic cells, CD49d loss altered leukemic cell localization in splenic niches. CD49d-deficient murine cells and human CD49d-low CLL cells could not form immune synapses to antigen-presenting membranes. CD49d-loss-related F-actin polymerization and transcriptomic defects in cytoskeleton-associated pathways were found in mouse and human. The requirement of CD49d for engraftment and actin organization could be recapitulated in a second murine model with highly aggressive transformed CLL. RNAseq analyses and kinome profiling revealed impaired antigen responsiveness due to kinase transcription and activity shifts in CD49d-deficient murine leukemic cells, recapitulated in human while applying several human BCR signatures. Finally, in human CLL expressing low CD49d, actin organization was deregulated, along with a desynchronization of Syk and PLCgamma activation. In summary, our findings establish CD49d as a key regulator of BCR functionality, linking integrin signaling to cytoskeletal dynamics and antigen responsiveness in CLL.

2026-07-29 | GSE301533 | GEO

Regulation of hTERT by BCR-ABL at multiple levels in K562 cells

Project description:To investigate the mechanism of telomerase regulation in BCR-ABL positive cells due to its clinical value, we studied the catalytic component of telomerase, TERT. Our results suggest that BCR-ABL plays an important role in regulating hTERT in K562 (BCR-ABL positive human leukemia) cells. When Gleevec inhibited the tyrosine kinase activity of BCR-ABL, phosphorylation of hTERT was downregulated, therefore suggesting a positive correlation between BCR-ABL and hTERT. Gleevec treatment inhibited hTERT at the mRNA level and significantly reduced telomerase activity (TA) in K562 cells, but not in HL60 or Jurkat cells. TRAP assay also revealed that Gleevec treatment significantly reduced TA specifically in K562 cells. Furthermore, translocation of hTERT from nucleoli to nucleoplasm was observed in K562 cells induced by Gleevec. Although Gleevec down-regulated hTERT mRNA level, the protein level of hTERT remained unchanged. Therefore, Gleevec-induced-TA decrease is not due to the alteration in telomerase subunits expression. It could be presumably due to posttranslational modification of hTERT, possibly through multiple signaling pathways. We have found that Gleevec reduced the tyrosine phosphorylation of hTERT by BCR-ABL, which is associated with the nucleoplasm localization of hTERT from nucleoli sequesters. These findings reveal unknown functions and regulations of telomerase by BCR-ABL. Using cRNA microarray, gene expression of Gleevec-treated and non-treated K562 (BCR-ABL positive) cells were compared against Gleevec-treated and non-treated HL60 (BCR-ABL deficient) cells.

2011-12-15 | E-GEOD-26821 | biostudies-arrayexpress

Csk restrains BCR-mediated ROS production and contributes to germinal center selection and affinity maturation

Project description:Compared with naïve B cells, the B cell receptor (BCR) signal in germinal center (GC) B cells is attenuated; however, the significance of this signaling attenuation has not been well defined. Here, to investigate the role of attenuation of BCR signaling, we employed a Csk mutant mouse model in which Csk-deficiency in GC B cells resulted in augmentation of net BCR signaling with no apparent effect on antigen presentation. We found that Csk is required for GC maintenance and efficient antibody affinity maturation. Mechanistically, ROS-induced apoptosis was exacerbated concomitantly with mitochondrial dysfunction in Csk-deficient GC B cells. Hence, our data suggest that attenuation of the BCR signal restrains hyper-ROS production, thereby protecting GC B cells from apoptosis and contributing to efficient affinity maturation.

2024-05-06 | GSE244802 | GEO

Zfx controls BCR-induced proliferation and survival of B lymphocytes

Project description:The development, homeostasis and function of B lymphocytes involve multiple rounds of B cell receptor (BCR)-controlled proliferation and prolonged maintenance. We analyzed the role of transcription factor Zfx, a recently identified regulator of stem cell maintenance, in B cell development and homeostasis. Conditional Zfx deletion in the bone marrow blocked B cell development at the pre-BCR selection checkpoint. Zfx deficiency in peripheral B cells caused impaired generation of the B-1 cell lineage, accelerated B cell turnover, depletion of mature recirculating cells, and delayed T-dependent antibody responses. Zfx-deficient B cells showed normal proximal BCR signaling, but impaired BCR-induced proliferation and survival. This was accompanied by aberrantly enhanced and prolonged integrated stress response, and delayed induction of Cyclin D2 and Bcl-xL proteins. Thus, Zfx restrains the stress response and couples antigen receptor signaling to B cell expansion and maintenance during development and peripheral homeostasis. Keywords: Expression profiling by array

2009-04-17 | GSE13547 | GEO

Antigen-selected gut IgA is generated from IgG1 germinal center B cells (BCR)

Project description:Antigen-selected gut IgA is generated from IgG1 germinal center B cells (BCR)

| PRJNA1199947 | ENA