Aleuria Aurantia Lectin (AAL)-Reactive Immunoglobulin G Rapidly Appears in Sera of Animals following Antigen Exposure

Songming Chen,Carthene R Bazemore-Walker,Timothy Block,Hongbo Gu,Chen Lu,David Horn,Patrick B Romano,D Craig Hooper,Jianwei Li,Anand Mehta

doi:10.1371/journal.pone.0044422

Abstract

We have discovered an Aleuria Aurantia Lectin (AAL)-reactive immunoglobulin G (IgG) that naturally occurs in the circulation of rabbits and mice, following immune responses induced by various foreign antigens. AAL can specifically bind to fucose moieties on glycoproteins. However, most serum IgGs are poorly bound by AAL unless they are denatured or treated with glycosidase. In this study, using an immunogen-independent AAL-antibody microarray assay that we developed, we detected AAL-reactive IgG in the sera of all animals that had been immunized 1–2 weeks previously with various immunogens with and without adjuvants and developed immunogen-specific responses. All of these animals subsequently developed immunogen-specific immune responses. The kinetics of the production of AAL-reactive IgG in mice and rabbits were distinct from those of the immunogen-specific IgGs elicited in the same animals: they rose and fell within one to two weeks, and peaked between four to seven days after exposure, while immunogen-specific IgGs continued to rise during the same period. Mass spectrometric profiling of the Fc glycoforms of purified AAL-reactive IgGs indicates that these are mainly comprised of IgGs with core-fucosylated and either mono-or non-galactosylated Fc N-glycan structures. Our results suggest that AAL-reactive IgG could be a previously unrecognized IgG subset that is selectively produced at the onset of a humoral response.

Highlights

Detection of exposure to pathogens or toxins is fundamental to medicine and public health [1,2], but can be challenging when the source and nature of a suspicious agent cannot be readily identified [3,4,5]
The limits of detection (LOD) are about 10.0 ng/ml in both assays, which is sufficient for the detection of the levels of Aurantia Lectin (AAL)-reactive IgG normally found in sera
While the concentration of total IgG remained constant, changes in the total level of all fucosylated glycoforms as well as that of AAL-reactive IgGs showed similar kinetics, both rapidly rising to peak approximately 10 days after immunization quickly falling (Figure 6). This is the first report of the induction by an immune response of an IgG that, in its native form, is bound by the fucose-selective lectin AAL

Summary

Introduction

Detection of exposure to pathogens or toxins is fundamental to medicine and public health [1,2], but can be challenging when the source and nature of a suspicious agent cannot be readily identified [3,4,5] This is mainly due to the inability of any detection system to detect exposure to all known and potential pathogens and agents of bioterrorism [2]. In this case, confirmation of exposure to a foreign substance or invading microbe may have utility in prompting intervention. An approach to confirm that an acute humoral immune response is underway would have therapeutic implications

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Results

Conclusion