PMID- 11496239 OWN - NLM STAT- MEDLINE DCOM- 20010906 LR - 20171116 IS - 0091-6749 (Print) IS - 0091-6749 (Linking) VI - 108 IP - 2 DP - 2001 Aug TI - Inhibition of IgE production in vitro by intact and fragmented intravenous immunoglobulin. PG - 229-34 AB - BACKGROUND: Intravenous immunoglobulin (IVIG) has been shown to suppress Ig production both in vivo and in vitro. We have previously found that IVIG inhibits IgE synthesis in human tonsillar B cells stimulated with IL-4 and anti-CD40 antibody. OBJECTIVE: The purpose of this study was to further clarify the mechanism behind the inhibition of IgE production by IVIG through comparing the effects of intact whole molecular IVIG and the F(ab')(2) or Fc fragments of IVIG. METHODS: Human B lymphocytes were purified from tonsils. Cell proliferation was measured by means of tritiated thymidine incorporation. IgE was determined by means of ELISA. Cell-cycle analysis was performed by using flow cytometry. RESULTS: Both intact and fractionated IVIG inhibited anti-CD40- and IL-4--stimulated IgE production in a dose-dependent manner. The maximal inhibition was achieved at 67 micromol/L (eg, 10, 6, and 4 mg/mL for intact IVIG, F[ab'](2), and Fc, respectively). The effect of F(ab')(2) was more pronounced than that of Fc at equimolar concentrations. Similarly, both intact and fragmented IVIG dose-dependently decreased tritiated thymidine incorporation. F(ab')(2) was also more potent than Fc in this effect. Heat-aggregated IVIG exhibited similar potency to regular IVIG in inhibiting B-cell proliferation. The inhibitory effects of IVIG were unlikely to have been caused by the induction of apoptosis because neither intact nor fractionated IVIG had a significant effect on cell-cycle parameters at the concentrations used. CONCLUSION: These data suggest that both F(ab')(2) and Fc portions contribute to the inhibition of in vitro IgE production by IVIG. The role of the F(ab')(2) portion is more important than that of the Fc portion. FAU - Zhuang, Q AU - Zhuang Q AD - Division of Allergy and Immunology, Montreal Children's Hospital, Meakins-Christie Laboratories, McGill University, Montreal, Quebec, Canada. FAU - Mazer, B AU - Mazer B LA - eng PT - Comparative Study 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 (Antibodies, Anti-Idiotypic) RN - 0 (CD40 Antigens) RN - 0 (Immunoglobulin Fab Fragments) RN - 0 (Immunoglobulin Fragments) RN - 0 (Immunoglobulins, Intravenous) RN - 0 (immunoglobulin Fv) RN - 207137-56-2 (Interleukin-4) RN - 37341-29-0 (Immunoglobulin E) SB - IM MH - Antibodies, Anti-Idiotypic MH - B-Lymphocytes/cytology/*drug effects MH - CD40 Antigens/metabolism MH - Cell Division/drug effects MH - Dose-Response Relationship, Drug MH - Humans MH - Immunoglobulin E/*biosynthesis MH - Immunoglobulin Fab Fragments/pharmacology MH - Immunoglobulin Fragments/*pharmacology MH - Immunoglobulins, Intravenous/*pharmacology MH - Interleukin-4/pharmacology MH - Models, Immunological EDAT- 2001/08/10 10:00 MHDA- 2001/09/08 10:01 CRDT- 2001/08/10 10:00 PHST- 2001/08/10 10:00 [pubmed] PHST- 2001/09/08 10:01 [medline] PHST- 2001/08/10 10:00 [entrez] AID - S0091-6749(01)90562-7 [pii] AID - 10.1067/mai.2001.116291 [doi] PST - ppublish SO - J Allergy Clin Immunol. 2001 Aug;108(2):229-34. doi: 10.1067/mai.2001.116291.