Project description:<p>To understand the genetic mechanisms driving variant and IGHV4-34 expressing hairy-cell leukemia, we performed whole exome sequencing of tumor/normal pairs from ten patients.</p>
Project description:<p>To understand the genetic mechanisms driving variant and IGHV4-34 expressing hairy-cell leukemia, we performed whole exome sequencing of tumor/normal pairs from ten patients.</p>
Project description:This single-cell RNA sequencing (scRNA-seq) dataset profiles human HCL cells from two patients with Hairy Cell Leukemia (HCL) and varient subtype of HCL (HCLv), both expressing unmutated IGHV4-34. scRNA-seq was performed on isolated CD19⁺ and CD3⁺cells from peripheral blood mononuclear cells (PBMC) (n=2). The dataset enables the characterization of expressed mutation and transcriptional profiles of human HCL cells and supports investigations into cellular lineage and pathways associated with pathologic activation leading to HCL and variant form of HCL (HCLv).
Project description:Preventing autoantibody secretion by rendering self-reactive B cells functionally silent through clonal anergy has long posed the question of why fill the circulating B cell repertoire with cells that cannot secrete antibody? Here we address this question from the perspective of B cells that comprise 5-10% of the human circulating repertoire, expressing self-reactive surface immunoglobulins employing the IGHV4-34 heavy chain variable element. Using gene targeting to construct mice expressing a representative human IGHV4-34 antibody on the surface of many B cells, we show these cells are prevented from autoantibody secretion by B cell clonal anergy marked by downregulation of surface IgM, induction of tolerance-response mRNAs, and exclusion from the marginal zone and B1 cell subsets. This functionally tolerant state is overridden when the IGHV4-34 B cells cross-react with a virus, which stimulates the self-reactive B cells to hypermutate in germinal centres. Within 16 days of infection, 99% of daughter cells have acquired one of five heavy chain mutations that diminish binding to self but preserve virus binding, and 33% had combined 2 or 3 of these mutations to become genetically self-tolerant and virus specific. These results demonstrate, from the perspective of a pathologically important human autoantibody class and the world’s most successful virus vaccine, how human antibody specificity is sculpted in the progeny of anergic B cells to yield antibodies that bind a virus but not self.
Project description:The hairy cell leukemia line JOK1 with low RhoH expression was stably trasfected with either an empty expression vector or this same vector expressing human RhoH. The transcriptomes of these two daughter lines were then compared by differential microarray analysis The hairy cell leukemia line JOK1 with low RhoH expression was stably trasfected with either an empty expression vector or this same vector expressing human RhoH. The transcriptomes of these two daughter lines were then compared by differential microarray analysis
