PMID- 18579794
OWN - NLM
STAT- MEDLINE
DCOM- 20080930
LR  - 20210206
IS  - 1528-0020 (Electronic)
IS  - 0006-4971 (Linking)
VI  - 112
IP  - 5
DP  - 2008 Sep 1
TI  - STAT3 is required for IL-21-induced secretion of IgE from human naive B cells.
PG  - 1784-93
LID - 10.1182/blood-2008-02-142745 [doi]
AB  - The production of immunoglobulin E (IgE) is tightly regulated. This is evidenced 
      by the fact that it comprises less than 0.0001% of serum Ig, and aberrant 
      production causes atopic conditions, including allergy, rhinitis, and 
      anaphylaxis. Interleukin-4 (IL-4) is a well-characterized inducer of IgE by human 
      and murine B cells, whereas interferon-gamma can antagonize this effect. IL-21 
      has also been recognized for its ability to suppress IL-4-induced IgE production 
      by murine B cells. Here, we identified IL-21 as an inducer of IgE production by 
      CD40L-stimulated human naive B cells. Furthermore, there was a striking synergy 
      between IL-4 and IL-21 on inducing IgE secretion by CD40L-stimulated human B 
      cells, such that the levels detected under these conditions exceeded those 
      induced by IL-4 or IL-21 alone by more than 10-fold. IL-21 induced activation of 
      STAT3 and analysis of B cells from patients with loss-of-function STAT3 mutations 
      revealed that the ability of IL-21 to induce IgE secretion, and augment that 
      driven by IL-4, was STAT3-dependent. These findings highlight a fundamental 
      difference between the regulation of IgE production by human and murine B cells 
      and have implications for the dysregulated production of IgE in conditions 
      characterized by extremely high levels of serum IgE.
FAU - Avery, Danielle T
AU  - Avery DT
AD  - Immunology and Inflammation Group, Garvan Institute of Medical Research, 
      Darlinghurst, NSW, Australia.
FAU - Ma, Cindy S
AU  - Ma CS
FAU - Bryant, Vanessa L
AU  - Bryant VL
FAU - Santner-Nanan, Brigitte
AU  - Santner-Nanan B
FAU - Nanan, Ralph
AU  - Nanan R
FAU - Wong, Melanie
AU  - Wong M
FAU - Fulcher, David A
AU  - Fulcher DA
FAU - Cook, Matthew C
AU  - Cook MC
FAU - Tangye, Stuart G
AU  - Tangye SG
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20080625
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (IL10 protein, human)
RN  - 0 (IL4 protein, human)
RN  - 0 (IL6 protein, human)
RN  - 0 (Interleukin-6)
RN  - 0 (Interleukins)
RN  - 0 (Receptors, IgE)
RN  - 0 (STAT3 Transcription Factor)
RN  - 0 (STAT3 protein, human)
RN  - 130068-27-8 (Interleukin-10)
RN  - 147205-72-9 (CD40 Ligand)
RN  - 207137-56-2 (Interleukin-4)
RN  - 37341-29-0 (Immunoglobulin E)
RN  - 82115-62-6 (Interferon-gamma)
RN  - MKM3CA6LT1 (interleukin-21)
SB  - IM
MH  - Animals
MH  - B-Lymphocytes/cytology/*drug effects/*immunology/physiology
MH  - CD4-Positive T-Lymphocytes/immunology
MH  - CD40 Ligand/pharmacology
MH  - Cell Differentiation
MH  - Cell Division
MH  - Cells, Cultured
MH  - Fetal Blood/cytology
MH  - Humans
MH  - Immunoglobulin E/*biosynthesis
MH  - In Vitro Techniques
MH  - Infant, Newborn
MH  - Interferon-gamma/biosynthesis
MH  - Interleukin-10/biosynthesis
MH  - Interleukin-4/physiology
MH  - Interleukin-6/physiology
MH  - Interleukins/chemistry/*pharmacology/physiology
MH  - Job Syndrome/genetics/immunology
MH  - Mice
MH  - Mutation
MH  - Phosphorylation
MH  - Receptors, IgE/metabolism
MH  - STAT3 Transcription Factor/deficiency/genetics/*physiology
MH  - Species Specificity
EDAT- 2008/06/27 09:00
MHDA- 2008/10/01 09:00
CRDT- 2008/06/27 09:00
PHST- 2008/06/27 09:00 [pubmed]
PHST- 2008/10/01 09:00 [medline]
PHST- 2008/06/27 09:00 [entrez]
AID - S0006-4971(20)49612-0 [pii]
AID - 10.1182/blood-2008-02-142745 [doi]
PST - ppublish
SO  - Blood. 2008 Sep 1;112(5):1784-93. doi: 10.1182/blood-2008-02-142745. Epub 2008 
      Jun 25.