Evidence that negative feedback between antibody concentration and affinity regulates humoral response consolidation to a non-infectious antigen in infants.
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 1 major 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 x 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.
The Asthma and Allergy Center, University of Minnesota Medical School, Minneapolis, Mayo Mail Code 434, 420 Delaware St. S.E., Minneapolis, MN 55455, USA. jacko001@umn.edu
Duaine R
DR
Jackola
Carol L
CL
Liebeler
Ching-Yuang
CY
Lin
Yi-Kai
YK
Chiu
Malcolm N
MN
Blumenthal
Andreas
A
Rosenberg
D000485:Allergens / Q000276:immunology*; D000818:Animals; D000906:Antibodies / Q000097:blood*; D000915:Antibody Affinity / Q000276:immunology*; D000917:Antibody Formation / Q000502:physiology*; D039741:Antigens, Dermatophagoides / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D025461:Feedback, Physiological / Q000276:immunology*; D006801:Humans; D007231:Infant, Newborn; D008962:Models, Theoretical; D011446:Prospective Studies; D039981:Pyroglyphidae / Q000276:immunology
D000485:Allergens; D000906:Antibodies; D039741:Antigens, Dermatophagoides