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.
Jackola
Duaine R
DR
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
Liebeler
Carol L
CL
Lin
Ching-Yuang
CY
Chiu
Yi-Kai
YK
Blumenthal
Malcolm N
MN
Rosenberg
Andreas
A
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