PMID- 12209098
OWN - NLM
STAT- MEDLINE
DCOM- 20021007
LR  - 20190723
IS  - 0091-6749 (Print)
IS  - 0091-6749 (Linking)
VI  - 110
IP  - 3
DP  - 2002 Sep
TI  - Suppression of IL-4- and CD40-induced B-lymphocyte activation by intravenous 
      immunoglobulin is not mediated through the inhibitory IgG receptor FcgammaRIIb.
PG  - 480-3
AB  - BACKGROUND: Intravenous immunoglobulin (IVIG) has been used extensively in the 
      treatment of autoimmune and allergic diseases, but the precise mechanism behind 
      its efficacy remains unclear. Ligation of the low-affinity IgG Fc receptor 
      FcgammaRIIb can inhibit B-lymphocyte activation. Our laboratory has shown that 
      IVIG suppresses proliferation and IgE production by human B cells stimulated with 
      IL-4 and anti-CD40 antibodies. OBJECTIVE: We sought to determine whether the 
      regulatory action of IVIG is mediated through binding FcgammaRIIb, 
      phosphorylation of the receptor, and induction of phosphatases, including 
      SH2-containing inositol-5'-phosphatase. METHODS: All experiments were performed 
      on human tonsillar B cells. Phenotyping was performed by means of flow cytometry. 
      Cells were cultured with IL-4 and anti-CD40 antibodies with or without IVIG (10 
      mg/mL), and FCgammaRIIb receptor activation and phosphorylation were measured by 
      means of Western blot analysis. RESULTS: FcgammaRIIb was the predominant isoform 
      of Fcgamma receptor expressed on tonsillar B cells, and preincubation with IVIG 
      failed to block binding of FcgammaRIIb antibody. Anti-FcgammaRIIb antibodies did 
      not reverse inhibition of B-cell proliferation or IgE production by IVIG. 
      Treatment of stimulated B lymphocytes with IVIG for 1 to 60 minutes did not 
      change the global protein tyrosine phosphorylation pattern, except for tyrosine 
      phosphorylation of an unidentified 30-kd protein. We directly examined tyrosine 
      phosphorylation of FcgammaRIIb and its downstream-associated phosphatase, 
      SH2-containing inositol-5'-phosphatase. Both remained unchanged after IVIG 
      treatment, as did other related phosphatases. CONCLUSION: These data argue 
      against the involvement of FcgammaRIIb in the inhibition of CD40/IL-4-induced 
      B-cell activation by IVIG.
FAU - Zhuang, Qianli
AU  - Zhuang Q
AD  - Division of Allergy and Immunology, Montreal Children's Hospital, McGill 
      University, Canada.
FAU - Bisotto, Sandra
AU  - Bisotto S
FAU - Fixman, Elizabeth D
AU  - Fixman ED
FAU - Mazer, Bruce
AU  - Mazer B
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Allergy Clin Immunol
JT  - The Journal of allergy and clinical immunology
JID - 1275002
RN  - 0 (Antigens, CD)
RN  - 0 (CD40 Antigens)
RN  - 0 (Fc gamma receptor IIB)
RN  - 0 (Immunoglobulins, Intravenous)
RN  - 0 (Phosphoproteins)
RN  - 0 (Receptors, IgG)
RN  - 207137-56-2 (Interleukin-4)
RN  - 21820-51-9 (Phosphotyrosine)
SB  - IM
MH  - Antigens, CD/*physiology
MH  - B-Lymphocytes/*immunology
MH  - CD40 Antigens/*metabolism
MH  - Cells, Cultured
MH  - Humans
MH  - Immunoglobulins, Intravenous/*pharmacology
MH  - Interleukin-4/*antagonists & inhibitors
MH  - Lymphocyte Activation
MH  - Phosphoproteins/analysis
MH  - Phosphotyrosine/metabolism
MH  - Receptors, IgG/metabolism/*physiology
EDAT- 2002/09/05 10:00
MHDA- 2002/10/09 04:00
CRDT- 2002/09/05 10:00
PHST- 2002/09/05 10:00 [pubmed]
PHST- 2002/10/09 04:00 [medline]
PHST- 2002/09/05 10:00 [entrez]
AID - S0091674902001392 [pii]
AID - 10.1067/mai.2002.127284 [doi]
PST - ppublish
SO  - J Allergy Clin Immunol. 2002 Sep;110(3):480-3. doi: 10.1067/mai.2002.127284.