The PDIA6 Knockout Raji Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population engineered for loss-of-function studies of PDIA6 (protein disulfide isomerase family A member 6). This product comprises a heterogeneous pool of Raji cells carrying CRISPR/Cas9-mediated gene disruption at the PDIA6 locus, providing a versatile model system to investigate PDIA6-dependent functions without the limitations of single clonal derivatives. The polyclonal format captures diverse editing events, enabling robust population-level analyses of PDIA6 roles in B-cell biology.
The host cell line, Raji, is a widely used human B lymphocyte model derived from an EBV-positive Burkitt??s lymphoma. These suspension-adapted cells exhibit features of mature B cells, including active immunoglobulin synthesis and secretion, making them an optimal system for studying ER protein folding, disulfide bond formation, and the unfolded protein response (UPR). The Raji background is particularly suited for dissecting the interplay between ER homeostasis and malignant B-cell phenotypes, including proliferation and apoptosis resistance.
PDIA6 functions as an ER-resident oxidoreductase that catalyzes disulfide bond formation and isomerization during protein folding, acting in concert with chaperones such as BiP/GRP78, calreticulin, and PDIA3. PDIA6 interacts directly with IRE1?? and ERdj3, modulating UPR signaling branches. Under ER stress, upstream transcription factors ATF6, XBP1, and ATF4 upregulate PDIA6 expression to restore proteostasis. Disruption of PDIA6 impairs the ER redox balance, leading to accumulation of misfolded proteins, hyperactivation of the PERK-eIF2??-ATF4-CHOP axis, and altered expression of BCL2 family proteins, thereby lowering the apoptotic threshold.
In Raji B cells, PDIA6 knockout profoundly disrupts ER homeostasis, given the high secretory burden imposed by immunoglobulin production. Loss of PDIA6 exacerbates UPR activation, as evidenced by increased XBP1 splicing, enhanced PERK signaling, and elevated CHOP levels, ultimately sensitizing cells to ER stress-induced apoptosis. The model recapitulates key aspects of proteotoxic stress observed in lymphomas, facilitating mechanistic studies of how lymphoid malignancies manage ER stress and evade cell death. It also enables the interrogation of PDIA6-specific contributions to antibody folding quality control and UPR regulation.
Researchers can employ PDIA6 Knockout Raji Polyclonal Cells in a broad range of experimental workflows, including Western blotting for UPR markers (BiP, CHOP, phospho-eIF2??), RT-qPCR for XBP1 splicing, flow cytometric apoptosis assays (Annexin V/PI), cell viability profiling under ER stress inducers (tunicamycin, thapsigargin), ER stress reporter assays, and immunofluorescence for ER morphology. Applications span the study of ER stress and UPR in B-cell lymphomas, drug sensitivity screening for ER stress modulators, functional analysis of PDIA6 in lymphoma progression, and investigation of disulfide bond formation in antibody production. For further information, please contact Ascent Research.
