title: Impaired Ig class switch in mice deficient for the X-linked lymphoproliferative disease gene Sap.
abstract: X-linked lymphoproliferative disease (XLP) is characterized by abnormal immune responses to Epstein-Barr virus attributed to inactivating mutations of the SAP gene. Previous studies showed immunoglobulin E (IgE) deficiency and low serum IgG levels in Sap-deficient mice before and after viral infections, which are associated with impaired CD4+ T-helper function. In the present work, we find that signaling lymphocytic activation molecule (SLAM)-associated protein (SAP) is expressed in B cells and this expression is down-regulated after stimulation with lipopolysaccharide (LPS) and interleukin 4 (IL-4). We demonstrate that B cells from Sap-deficient mice exhibit reduced IgG and IgA production in vitro. This impairment correlates with decreased circular transcript levels of Ialpha, Igamma2a, Igamma2b, and Igamma3 after stimulation, which indicate a defective Ig switch recombination in Sap-deficient B cells. While XLP is believed to cause defects in T, natural killer T (NKT), and natural killer (NK) cells, our results indicate that B cells are also affected.
authors.affiliation: International Agency for Research on Cancer, Lyon, France.
authors.forename: Umaima
authors.initials: U
authors.lastname: Al-Alem
authors.forename: Cuiling
authors.initials: C
authors.lastname: Li
authors.forename: Nathalie
authors.initials: N
authors.lastname: Forey
authors.forename: Francis
authors.initials: F
authors.lastname: Relouzat
authors.forename: Marie-Claude
authors.initials: MC
authors.lastname: Fondanèche
authors.forename: Sean V
authors.initials: SV
authors.lastname: Tavtigian
authors.forename: Zhao-Qi
authors.initials: ZQ
authors.lastname: Wang
authors.forename: Sylvain
authors.initials: S
authors.lastname: Latour
authors.forename: Luo
authors.initials: L
authors.lastname: Yin
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D015536:Down-Regulation / Q000187:drug effects; D007070:Immunoglobulin A / Q000096:biosynthesis; D017578:Immunoglobulin Class Switching; D007074:Immunoglobulin G / Q000096:biosynthesis; D015847:Interleukin-4 / Q000494:pharmacology; D047908:Intracellular Signaling Peptides and Proteins / Q000172:deficiency* / Q000235:genetics; D008070:Lipopolysaccharides / Q000494:pharmacology; D008232:Lymphoproliferative Disorders / Q000235:genetics / Q000276:immunology*; D051379:Mice; D012333:RNA, Messenger / Q000032:analysis; D000071179:Signaling Lymphocytic Activation Molecule Associated Protein
chemical_list: D007070:Immunoglobulin A; D007074:Immunoglobulin G; D047908:Intracellular Signaling Peptides and Proteins; D008070:Lipopolysaccharides; D012333:RNA, Messenger; C499569:Sh2d1a protein, mouse; D000071179:Signaling Lymphocytic Activation Molecule Associated Protein; D015847:Interleukin-4