A Glycoform of Immunoglobulin G (IgG) as an Early Biomarker of Exposure to Nonhuman Substances

Abstract

Abstract : We have identified an immunoglobulin G (IgG) subset that transiently exists in rabbits and mice following the introduction of various nonself antigens. This previously unrecognized IgG was named primebody because it appears to be involved in priming the humoral immune response rather than in neutralizing immunogens. Primebody was initially identified by its ability to bind the Aleuria aurantia lectin (AAL) while still in its native conformation, in contrast to serum IgGs that bind AAL poorly, unless denatured. For both animals inoculated with three different immunogens, serum levels of primebody that were investigated with an AAL-antibody microarray assay reached peak levels 5 to 16 days post-inoculation. However, the immunogen-specific IgG levels peaked much later, between 21 to 60 days post-inoculation. Mass spectrometry analysis revealed 22 different primebody glycoisoforms in rabbits, all of which were under-galactosylated IgG (G0 and G1) with core fucose on its constant region N-glycan. We hypothesized that the immunoglobulin constant region heavy chain 2 (CH2) domain of primebody adopts an open conformation that allows AAL complete access to its glycans, in contrast with the usual closed conformation adopted by immunoglobulin CH2 domains, which are known to deny all glycan access.