Rogosch, Tobias and Kerzel, Sebastian and Dey, Friederike and Wagner, Johanna-Josophina and Zhang, Zhixin and Maier, Rolf F. and Zemlin, Michael (2014) IgG4 and IgE Transcripts in Childhood Allergic Asthma Reflect Divergent Antigen-Driven Selection. JOURNAL OF IMMUNOLOGY, 193 (12). pp. 5801-5808. ISSN 0022-1767, 1550-6606
Full text not available from this repository. (Request a copy)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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | FAB-ARM EXCHANGE; EFFECTOR CELL DEGRANULATION; HUMAN B-CELLS; GRASS-POLLEN; SOMATIC HYPERMUTATION; DISTINCT REGULATION; GENE REARRANGEMENT; IMMUNOGLOBULIN G4; IGG(4) ANTIBODIES; BLOOD-LYMPHOCYTES; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Kinder- und Jugendmedizin |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 05 Aug 2019 13:38 |
| Last Modified: | 05 Aug 2019 13:38 |
| URI: | https://pred.uni-regensburg.de/id/eprint/9048 |
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