Evidence that negative feedback between antibody concentration and affinity regulates humoral response consolidation to a non-infectious antigen in infants

Duaine R. Jackola, Carol L. Liebeler, Ching Yuang Lin, Yi Kai Chiu, Malcolm N Blumenthal, Andreas Rosenberg

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

The dynamics of human antigen-specific immunoglobulin (Ig) responses in early life are not well characterized. We have previously observed an inverse relationship between allergen-specific Ig concentration and allergen-Ig-binding affinity in allergen-sensitive atopic adults, suggesting a possible feedback relationship between these variables. We prospectively studied children (6 months to 6 years) with and without atopic sensitization to the Der p 1major allergen. Experimental results showed the following trends. (1) In both study groups, there was little change with age in average Der p 1-specific Ig (IgG1 or IgE) concentrations or allergen-Ig-binding affinities, and concentrations and affinities were independent. (2) Among individuals, however, there was a negative correlation between Ig concentration changes and affinity changes with age. (3) The rate of increase with age of the non-atopic Der p 1-IgG1 total binding capacity (Ig concentration × Ig affinity) paralleled that for the atopic Der p 1-IgE total binding capacity, and there was a comparable "consolidation" of responses with age reflected by a narrowing of the variance of total binding capacity values. Except for the Ig classes involved, development of a humoral response to a non-infectious allergen is similarly regulated in atopic and non-atopic children, with Ig total binding capacity as the key regulatory variable. These results also suggest that there is a time-dependent feedback relationship between Ig concentrations and affinities that establishes an optimal Ig total binding capacity for a given environmental "antigen load". A theoretical model is proposed to account for this relationship.

Original languageEnglish (US)
Pages (from-to)19-30
Number of pages12
JournalMolecular Immunology
Volume42
Issue number1
DOIs
StatePublished - Jan 1 2005

Keywords

  • Affinity
  • Allergen
  • Antibodies
  • Atopy
  • Human
  • IgE
  • IgG1

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