Anti-Human BCL2L1 (Phospho-Thr115) polyclonal antibody

Stroke is one of the most destructive complications of sickle cell disease (SCD), and SCD is also the most common cause of childhood stroke. Sickle cell stroke is complex and has a genetic endothelial basis. Here, we further investigated this genetic basis using weighted gene coexpression network analysis. This systems biology approach revealed the correlation between coexpressed gene modules and sickle stroke risk. The pink module was significantly correlated with stroke risk and genes in this module were mainly related to GO:0044877 (protein-containing complex binding). In addition hub genes were identified through protein-protein interaction enrichment analysis, including CXCR7, VCAM1, CD44, BMP2, SMAD3, BCL2L1, ITPR2, ITPR3, etc. These hub genes were significantly enriched for three Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways including "gastric acid secretion," "pathways in cancer," and "TGF- beta signaling pathway." Altogether, our results based on this innovative method provided some novel understanding of the pathology of sickle cell stroke. Hub genes identified in this study could be potential targets for screening and prevention of stroke risk in SCD children.

BTB and CNC homology 2 (Bach2) is a transcriptional repressor that is required for the formation of the germinal center (GC) and reactions, including class switch recombination and somatic hypermutation of Ig genes in B cells, within the GC. Although BCR-induced proliferation is essential for GC reactions, the function of Bach2 in regulating B cell proliferation has not been elucidated. In this study, we demonstrate that Bach2 is required to sustain high levels of B cell proliferation in response to BCR signaling. Following BCR engagement in vitro, B cells from Bach2-deficient (Bach2(-/-)) mice showed lower incorporation of BrdU and reduced cell cycle progression compared with wild-type cells. Bach2(-/-) B cells also underwent increased apoptosis, as evidenced by an elevated frequency of sub-G(1) cells and early apoptotic cells. Transcriptome analysis of BCR-engaged B cells from Bach2(-/-) ice revealed reduced expression of the antiapoptotic gene Bcl2l1 encoding Bcl-x(L) and elevated expression of cyclin-dependent kinase inhibitor (CKI) family genes, including Cdkn1a, Cdkn2a, and Cdkn2b. Reconstitution of Bcl-xL expression partially rescued the proliferation defect of Bach2(-/-) B cells. Chromatin immunoprecipitation experiments showed that Bach2 bound to the CKI family genes, indicating that these genes are direct repression targets of Bach2. These findings identify Bach2 as a requisite factor for sustaining high levels of BCR-induced proliferation, survival, and cell cycle progression, and it promotes expression of Bcl-x(L) and repression of CKI genes. BCR-induced proliferation defects may contribute to the impaired GC formation observed in Bach2(-/-) mice.