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

• Published in: Molecular immunology 2005, Vol.42 (1), p.19-30
• Main Authors: Jackola, Duaine R., Liebeler, Carol L., Lin, Ching-Yuang, Chiu, Yi-Kai, Blumenthal, Malcolm N., Rosenberg, Andreas
• Format: Article
• Language: English
• Subjects: Affinity; Allergen; Allergens - immunology; Animals; Antibodies; Antibodies - blood; Antibody Affinity - immunology; Antibody Formation - physiology; Antigens, Dermatophagoides - immunology; Atopy; Child; Child, Preschool; Feedback, Physiological - immunology; Human; Humans; IgE; IgG1; Infant, Newborn; Models, Theoretical; Prospective Studies; Pyroglyphidae - immunology
• ISSN: 0161-5890; 1872-9142
• DOI: 10.1016/j.molimm.2004.07.006

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.