PMID- 15941917
OWN - NLM
STAT- MEDLINE
DCOM- 20051011
LR  - 20210206
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 106
IP  - 6
DP  - 2005 Sep 15
TI  - Impaired Ig class switch in mice deficient for the X-linked lymphoproliferative 
      disease gene Sap.
PG  - 2069-75
AB  - 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.
FAU - Al-Alem, Umaima
AU  - Al-Alem U
AD  - International Agency for Research on Cancer, Lyon, France.
FAU - Li, Cuiling
AU  - Li C
FAU - Forey, Nathalie
AU  - Forey N
FAU - Relouzat, Francis
AU  - Relouzat F
FAU - Fondaneche, Marie-Claude
AU  - Fondaneche MC
FAU - Tavtigian, Sean V
AU  - Tavtigian SV
FAU - Wang, Zhao-Qi
AU  - Wang ZQ
FAU - Latour, Sylvain
AU  - Latour S
FAU - Yin, Luo
AU  - Yin L
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20050607
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (Immunoglobulin A)
RN  - 0 (Immunoglobulin G)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (RNA, Messenger)
RN  - 0 (Sh2d1a protein, mouse)
RN  - 0 (Signaling Lymphocytic Activation Molecule Associated Protein)
RN  - 207137-56-2 (Interleukin-4)
SB  - IM
MH  - Animals
MH  - B-Lymphocytes/immunology/metabolism/*pathology
MH  - Down-Regulation/drug effects
MH  - Immunoglobulin A/biosynthesis
MH  - *Immunoglobulin Class Switching
MH  - Immunoglobulin G/biosynthesis
MH  - Interleukin-4/pharmacology
MH  - Intracellular Signaling Peptides and Proteins/*deficiency/genetics
MH  - Lipopolysaccharides/pharmacology
MH  - Lymphoproliferative Disorders/genetics/*immunology
MH  - Mice
MH  - RNA, Messenger/analysis
MH  - Signaling Lymphocytic Activation Molecule Associated Protein
EDAT- 2005/06/09 09:00
MHDA- 2005/10/12 09:00
CRDT- 2005/06/09 09:00
PHST- 2005/06/09 09:00 [pubmed]
PHST- 2005/10/12 09:00 [medline]
PHST- 2005/06/09 09:00 [entrez]
AID - S0006-4971(20)63430-9 [pii]
AID - 10.1182/blood-2004-07-2731 [doi]
PST - ppublish
SO  - Blood. 2005 Sep 15;106(6):2069-75. doi: 10.1182/blood-2004-07-2731. Epub 2005 Jun 
      7.