Anti-BCR (full length) polyclonal antibody

The IKZF1 gene, which encodes the Ikaros transcription factor, is frequently deleted or mutated in patients with B-cell precursor acute lymphoblastic leukemias that express oncogenes, like BCR-ABL, which activate the JAK-STAT5 pathway. Ikaros functionally antagonizes the transcriptional programs downstream of IL-7/STAT5 during B cell development, as well as STAT5 activity in leukemic cells. However, the mechanisms by which Ikaros interferes with STAT5 function is unknown. We studied the genomic distribution of Ikaros and STAT5 on chromatin in a murine pre-B cell line, and found that both proteins colocalize on >60% of STAT5 target regions. Strikingly, Ikaros activity leads to widespread loss of STAT5 binding at most of its genomic targets within two hours of Ikaros induction, suggesting a direct mechanism. Ikaros did not alter the level of total or phosphorylated STAT5 proteins, nor did it associate with STAT5. Using sequences from the Cish, Socs2 and Bcl6 genes that Ikaros and STAT5 target, we show that both proteins bind overlapping sequences at GGAA motifs. Our results demonstrate that Ikaros antagonizes STAT5 DNA binding, in part by competing for common target sequences. Our study has implications for understanding the functions of Ikaros and STAT5 in B cell development and transformation.

Immunoglobulin (Ig) A nephropathy (IgAN) is the most common glomerulonephritis, which is characterized by the deposition of IgA antibody in the glomerulus. Systematic dissection of immune composition may contribute to a better understanding of the alternations in the immune system in IgAN. To this end, here we applied immune repertoire sequencing technology for parallel analysis of the complementary determining region 3 (CDR3) of all B cell receptors, including all five antibody subtypes (IgA, IgG, IgM, IgE and IgD), in 13 patients with IgAN and 7 healthy individuals. A significant decrease in CDR3 length was observed in the IgAN group. In particular, the JH6 family was significantly increased in IgAN. Amino acid usage was also altered in IgAN. Shannon, Simpson, Gini and Diversity 50 indices also revealed significant differences in the diversity of IgG, IgM and IgA antibodies as compared with controls. The proportions of IgA and IgG were increased, whereas IgM was decreased in IgAN. Moreover, a greater number of CDR3 sequences was shared between patients with IgAN. These findings suggest that the BCR immune repertoire is dramatically altered in IgAN, as characterized by shortened CDR3 length, as well as decreased overall diversity of CDR3.