NDLI: IgG4 and IgE transcripts in childhood allergic asthma reflect divergent antigen-driven selection.

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IgG4 and IgE transcripts in childhood allergic asthma reflect divergent antigen-driven selection.

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IgG4 and IgE transcripts in childhood allergic asthma reflect divergent antigen-driven selection.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Zemlin, Michael Maier, Rolf F. Kerzel, Sebastian Rogosch, Tobias Zhang, Zhixin Wagner, Johanna-Josophina Dey, Friederike
Description	Author Affiliation: Rogosch T ( Department of Pediatrics, Philipps-University Marburg, D-35033 Marburg, Germany); Kerzel S ( Department of Pediatric Pneumology and Allergy, University Children's Hospital Regensburg, St. Hedwig Campus, 93053 Regensburg, Germany); Dey F ( Department of Pediatrics, Philipps-University Marburg, D-35033 Marburg, Germany); Wagner JJ ( Department of Pediatrics, Philipps-University Marburg, D-35033 Marburg, Germany); Zhang Z ( Department of Pathology and Microbiology, Eppley Institute for Research in Cancer, University of Nebraska Medical Center, Omaha, NE 68198.); Maier RF ( Department of Pediatrics, Philipps-University Marburg, D-35033 Marburg, Germany); Zemlin M ( Department of Pediatrics, Philipps-University Marburg, D-35033 Marburg, Germany)
Abstract	The physiologic function of the 'odd' Ab IgG4 remains enigmatic. IgG4 mediates immunotolerance, as, for example, during specific immunotherapy of allergies, but it mediates tissue damage in autoimmune pemphigus vulgaris and 'IgG4-related disease.' Approximately half of the circulating IgG4 molecules are bispecific owing to their unique ability to exchange half-molecules. Better understanding of the interrelation between IgG4 and IgE repertoires may yield insight into the pathogenesis of allergies and into potential novel therapies that modulate IgG4 responses. We aimed to compare the selective forces that forge the IgG4 and IgE repertoires in allergic asthma. Using an IgG4-specific RT-PCR, we amplified, cloned, and sequenced IgG4 H chain transcripts of PBMCs from 10 children with allergic asthma. We obtained 558 functional IgG4 sequences, of which 286 were unique. Compared with previously published unique IgE transcripts from the same blood samples, the somatic mutation rate was significantly enhanced in IgG4 transcripts (62 versus 83%; p < 0.001), whereas fewer IgG4 sequences displayed statistical evidence of Ag-driven selection (p < 0.001). On average, the hypervariable CDRH3 region was four nucleotides shorter in IgG4 than in IgE transcripts (p < 0.001). IgG4 transcripts in the circulation of children with allergic asthma reflect some characteristics of classical Ag-driven B2 immune responses but display less indication of Ag selection than do IgE transcripts. Although allergen-specific IgG4 can block IgE-mediated allergen presentation and degranulation of mast cells, key factors that influence the Ag-binding properties of the Ab differ between the overall repertoires of circulating IgG4- and IgE-expressing cells.
ISSN	00221767
e-ISSN	15506606
Journal	The Journal of Immunology
Issue Number	12
Volume Number	193
Language	English
Publisher	The American Association of Immunologists
Publisher Date	2014-12-15
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Antigens Immunology Asthma Genetics Immunoglobulin E Immunoglobulin G Transcription, Genetic Adolescent Allergens B-lymphocytes Metabolism Child, Preschool Complementarity Determining Regions Chemistry Classification Immunoglobulin Heavy Chains Immunoglobulin J-chains Molecular Sequence Data Mutation Mutation Rate Phylogeny Research Support, Non-u.s. Gov't Discipline Immunology
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology

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