PMID- 9058789
OWN - NLM
STAT- MEDLINE
DCOM- 19970402
LR  - 20171116
IS  - 0022-1767 (Print)
IS  - 0022-1767 (Linking)
VI  - 158
IP  - 6
DP  - 1997 Mar 15
TI  - Abnormal CD40-mediated activation pathway in B lymphocytes from patients with 
      hyper-IgM syndrome and normal CD40 ligand expression.
PG  - 2576-84
AB  - The CD40-mediated activation pathway of B cells from 10 patients with hyper-IgM 
      syndrome and normal expression of CD40 ligand was studied. In all 10 cases, B 
      cells were found to be defective for IgG, IgA, and IgE production after 
      stimulation by anti-CD40 mAbs and cytokines. In the patients tested, neither B 
      cell proliferation (n = 6) nor CD23 molecule expression (n = 5) were observed in 
      cultures stimulated with anti-CD40 mAb. These results point to an intrinsic B 
      cell deficiency and a defect in the CD40-triggered B cell activation pathway; 
      this conclusion was supported by a lack of detectable germinal centers in the 
      spleen of two patients. CD40-triggered activation events, i.e., 
      phosphatidylinositol 3 (PI3) kinase activation and induction of transcription 
      factors NF-kappaB and AP-1, were next analyzed in B cell lines derived from five 
      patients. Three distinct patterns were observed: an absence of detectable 
      abnormalities (n = 1), defective PI3 kinase activation with normal induction of 
      NF-kappaB and AP-1 (n = 3), and defects in both PI3 kinase activation and 
      induction of NF-kappaB and AP-1 (n = 1). In three B cell lines, each exhibiting 
      one of the CD40-mediated activation patterns, sequences of CD40 and CD40 binding 
      protein coding regions were normal. The coding region of TNF receptor-associated 
      factor 2 (TRAF2), which is known to interact with CD40 for NF-kappaB induction, 
      was also found to be normal in B cell lines deficient in NF-kappaB induction. 
      Altogether, these results suggest that CD40 ligand-positive hyper-IgM syndrome 
      could be genetically heterogeneous, although phenotypic variability is not 
      excluded, and that an early defect in the CD40-triggered activation cascade can 
      account for defective Ig class switching in some patients with CD40 
      ligand-positive hyper-IgM syndrome.
FAU - Durandy, A
AU  - Durandy A
AD  - INSERM Unit 429, Hospital Necker-Enfants Malades, Paris, France. 
      durandy@ceylan.necker.fr
FAU - Hivroz, C
AU  - Hivroz C
FAU - Mazerolles, F
AU  - Mazerolles F
FAU - Schiff, C
AU  - Schiff C
FAU - Bernard, F
AU  - Bernard F
FAU - Jouanguy, E
AU  - Jouanguy E
FAU - Revy, P
AU  - Revy P
FAU - DiSanto, J P
AU  - DiSanto JP
FAU - Gauchat, J F
AU  - Gauchat JF
FAU - Bonnefoy, J Y
AU  - Bonnefoy JY
FAU - Casanova, J L
AU  - Casanova JL
FAU - Fischer, A
AU  - Fischer A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (CD40 Antigens)
RN  - 0 (Carrier Proteins)
RN  - 0 (Codon)
RN  - 0 (DNA, Complementary)
RN  - 0 (Immunoglobulin M)
RN  - 0 (Ligands)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (TNF Receptor-Associated Factor 3)
RN  - 0 (TRAF3 protein, human)
RN  - 0 (Tumor Necrosis Factor Receptor-Associated Peptides and Proteins)
RN  - 147205-72-9 (CD40 Ligand)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - B-Lymphocytes/*immunology
MH  - CD40 Antigens/*biosynthesis/genetics/*physiology
MH  - CD40 Ligand
MH  - Carrier Proteins/genetics
MH  - Child
MH  - Child, Preschool
MH  - Codon/analysis
MH  - DNA, Complementary/analysis
MH  - Female
MH  - Humans
MH  - Hypergammaglobulinemia/*immunology
MH  - *Immunoglobulin M
MH  - Intracellular Fluid/immunology
MH  - Ligands
MH  - *Lymphocyte Activation
MH  - Male
MH  - Membrane Glycoproteins/immunology
MH  - Middle Aged
MH  - Syndrome
MH  - TNF Receptor-Associated Factor 3
MH  - *Tumor Necrosis Factor Receptor-Associated Peptides and Proteins
EDAT- 1997/03/15 00:00
MHDA- 1997/03/15 00:01
CRDT- 1997/03/15 00:00
PHST- 1997/03/15 00:00 [pubmed]
PHST- 1997/03/15 00:01 [medline]
PHST- 1997/03/15 00:00 [entrez]
PST - ppublish
SO  - J Immunol. 1997 Mar 15;158(6):2576-84.