""B-cells, which are responsible for producing antibodies, rely on BCRs for survival and growth. While most research has focused on the IgM variant of BCRs, this study sheds light on the lesser-understood IgG1 variant," said Vipul Shukla, PhD, assistant professor of Cell and Developmental Biology, who was co-senior author of the study. "Our lab focuses on understanding the molecular control of B-cell function, which are a key component of the immune system responsible for generating antibodies,""
"The study was inspired by a longstanding clinical observation: patients with B-cell lymphomas expressing IgG BCRs tend to have better outcomes than those with IgM BCRs. To investigate this, investigators engineered lymphoma cells to express either IgM or IgG1 BCRs and analyzed their behavior. The scientists observed that IgG1 BCRs triggered enhanced calcium signaling, which leads to mitochondrial dysfunction and reduced cell survival. However, this effect could be reversed."
Lymphoma cells engineered to express either IgM or IgG1 B-cell receptors exhibited distinct signaling and survival behaviors. Cells with IgG1 BCRs generated enhanced calcium signaling that induced mitochondrial dysfunction and decreased cell survival. The survival defect in IgG1-expressing cells could be reversed under certain conditions. Clinical observations associate IgG BCR expression in B-cell lymphomas with better patient outcomes compared with IgM expression. Current targeted therapies for B-cell cancers focus on suppressing BCR signaling and are mostly informed by knowledge of IgM-driven signaling. Differences between IgM and IgG1 BCR signaling reveal alternative vulnerabilities that could guide more tailored therapeutic approaches.
#diffuse-large-b-cell-lymphoma #b-cell-receptor-signalling #igg1-vs-igm-bcr #calcium-signaling #mitochondrial-dysfunction
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