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Title: Lymphocyte-Specific Protein Tyrosine Kinase (LCK) is Involved in the Aryl Hydrocarbon Receptor-Mediated Impairment of Immunoglobulin Secretion in Human Primary B Cells.

Authors: Zhou, Jiajun; Zhang, Qiang; Henriquez, Joseph E; Crawford, Robert B; Kaminski, Norbert E

Published In Toxicol Sci, (2018 10 01)

Abstract: The aryl hydrocarbon receptor (AHR) is a cytosolic ligand-activated transcription factor involved in xenobiotic sensing, cell cycle regulation, and cell development. In humans, the activation of AHR by 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), a high affinity AHR-ligand, impairs the secretion of immunoglobulin M (IgM) to suppress humoral immunity. However, the mechanisms bridging the activation of AHR and the impairment of IgM secretion by human primary B cells remain poorly understood. Recent transcriptomic analysis revealed upregulation of lymphocyte-specific protein tyrosine kinase (LCK) in AHR-activated human primary B cells. LCK is a well-characterized tyrosine kinase that phosphorylates critical signaling proteins involved in activation and cytokine production in T cells. Conversely, the role of LCK in human primary B cells is not well understood. In the current studies, we have verified the transcriptomic finding by detecting AHR-mediated upregulation of LCK protein in human primary B cells. We also confirmed the role of AHR in the upregulation of LCK by using a specific AHR antagonist, which abolished the AHR-mediated increase of LCK. Furthermore, we have confirmed the role of LCK in the AHR-mediated suppression of IgM by using LCK specific inhibitors, which restored the IgM secretion by human B cells in the presence of TCDD. Collectively, the current studies demonstrate a novel role of LCK in IgM response and provide new insights into the mechanism for AHR-mediated impairment of immunoglobulin secretion by human primary B cells.

PubMed ID: 29860352 Exiting the NIEHS site

MeSH Terms: B-Lymphocytes/drug effects*; B-Lymphocytes/enzymology; B-Lymphocytes/metabolism*; Basic Helix-Loop-Helix Transcription Factors/metabolism*; Cells, Cultured; Humans; Immunoglobulin M/metabolism*; Lymphocyte Activation/drug effects; Lymphocyte Specific Protein Tyrosine Kinase p56(lck)/metabolism*; Polychlorinated Dibenzodioxins/toxicity; Primary Cell Culture; Receptors, Aryl Hydrocarbon/metabolism*

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