title: B-1 cell lymphoma in mice lacking the steroid and xenobiotic receptor, SXR.
abstract: The steroid and xenobiotic receptor (SXR) is a broad-specificity nuclear hormone receptor that is highly expressed in the liver and intestine, where its primary function is to regulate drug and xenobiotic metabolism. SXR is expressed at lower levels in other tissues, where little is known about its physiological functions. We previously linked SXR with immunity and inflammation by showing that SXR antagonizes the activity of nuclear factor (NF)-κB in vitro and in vivo. SXR(-/-) mice demonstrate aberrantly high NF-κB activity and overexpression of NF-κB target genes. Here we show that SXR(-/-) mice develop B cell lymphoma in an age-dependent manner. SXR(-/-) mice develop multiple hyperplastic lymphoid foci composed of B-1a cells in the intestine, spleen, lymph nodes, peritoneal cavity, and blood. In all circumstances, these lymphocytes possess cell surface and molecular characteristics of either chronic lymphocytic leukemia or non-Hodgkin's lymphoma originating from B-1 lymphocytes. These results demonstrate a novel and unsuspected role for SXR signaling in the B-1 cell compartment, establish SXR as a tumor suppressor in B-1 cells, and may provide a link between metabolism of xenobiotic compounds and lymphomagenesis.
authors: Developmental and Cell Biology, University of California, Irvine, California 92697-2300, USA.
authors: Stephanie C
authors: SC
authors: Casey
authors: Edward L
authors: EL
authors: Nelson
authors: Gina M
authors: GM
authors: Turco
authors: Matthew R
authors: MR
authors: Janes
authors: David A
authors: DA
authors: Fruman
authors: Bruce
authors: B
authors: Blumberg
mesh_terms: D000367:Age Factors; D000818:Animals; D017209:Apoptosis; D016175:B-Lymphocyte Subsets / Q000378:metabolism / Q000473:pathology; D018956:CD5 Antigens / Q000378:metabolism; D049109:Cell Proliferation; D002478:Cells, Cultured; D005260:Female; D007075:Immunoglobulin M / Q000378:metabolism; D007422:Intestines / Q000473:pathology; D037102:Lectins / Q000235:genetics / Q000378:metabolism; D017493:Leukocyte Common Antigens / Q000378:metabolism; D008198:Lymph Nodes / Q000473:pathology; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000235:genetics / Q000378:metabolism; D008214:Lymphocytes / Q000473:pathology; D016393:Lymphoma, B-Cell / Q000235:genetics* / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D016513:Mice, SCID; D016328:NF-kappa B / Q000378:metabolism; D009368:Neoplasm Transplantation; D000077297:Pregnane X Receptor; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6 / Q000235:genetics / Q000378:metabolism; D011947:Receptors, Antigen, B-Cell / Q000235:genetics / Q000378:metabolism; D011987:Receptors, Steroid / Q000235:genetics* / Q000378:metabolism; D063265:Sialic Acid Binding Immunoglobulin-like Lectins; D013154:Spleen / Q000473:pathology; D014158:Transcription, Genetic; D051746:ZAP-70 Protein-Tyrosine Kinase / Q000235:genetics / Q000378:metabolism; D005719:gamma-Globulins / Q000378:metabolism
chemical_list: D018956:CD5 Antigens; C526836:Cd5 protein, mouse; D007075:Immunoglobulin M; D037102:Lectins; D016328:NF-kappa B; D000077297:Pregnane X Receptor; D011947:Receptors, Antigen, B-Cell; D011987:Receptors, Steroid; D063265:Sialic Acid Binding Immunoglobulin-like Lectins; C522403:Siglecg protein, mouse; D005719:gamma-Globulins; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D051746:ZAP-70 Protein-Tyrosine Kinase; C497262:Zap70 protein, mouse; D017493:Leukocyte Common Antigens; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; C509248:Ptpn6 protein, mouse