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Fab-dimerized glycan-reactive antibodies are a structural category of natural antibodies.

ABSTRACT: Natural antibodies (Abs) can target host glycans on the surface of pathogens. We studied the evolution of glycan-reactive B cells of rhesus macaques and humans using glycosylated HIV-1 envelope (Env) as a model antigen. 2G12 is a broadly neutralizing Ab (bnAb) that targets a conserved glycan patch on Env of geographically diverse HIV-1 strains using a unique heavy-chain (V_H) domain-swapped architecture that results in fragment antigen-binding (Fab) dimerization. Here, we describe HIV-1 Env Fab-dimerized glycan (FDG)-reactive bnAbs without V_H-swapped domains from simian-human immunodeficiency virus (SHIV)-infected macaques. FDG Abs also recognized cell-surface glycans on diverse pathogens, including yeast and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike. FDG precursors were expanded by glycan-bearing immunogens in macaques and were abundant in HIV-1-naive humans. Moreover, FDG precursors were predominately mutated IgM⁺IgD⁺CD27⁺, thus suggesting that they originated from a pool of antigen-experienced IgM⁺ or marginal zone B cells.

SUBMITTER: Williams WB

PROVIDER: S-EPMC8135257 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature

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Fab-dimerized glycan-reactive antibodies are a structural category of natural antibodies.

Williams Wilton B WB Meyerhoff R Ryan RR Edwards R J RJ Li Hui H Manne Kartik K Nicely Nathan I NI Henderson Rory R Zhou Ye Y Janowska Katarzyna K Mansouri Katayoun K Gobeil Sophie S Evangelous Tyler T Hora Bhavna B Berry Madison M Abuahmad A Yousef AY Sprenz Jordan J Deyton Margaret M Stalls Victoria V Kopp Megan M Hsu Allen L AL Borgnia Mario J MJ Stewart-Jones Guillaume B E GBE Lee Matthew S MS Bronkema Naomi N Moody M Anthony MA Wiehe Kevin K Bradley Todd T Alam S Munir SM Parks Robert J RJ Foulger Andrew A Oguin Thomas T Sempowski Gregory D GD Bonsignori Mattia M LaBranche Celia C CC Montefiori David C DC Seaman Michael M Santra Sampa S Perfect John J Francica Joseph R JR Lynn Geoffrey M GM Aussedat Baptiste B Walkowicz William E WE Laga Richard R Kelsoe Garnett G Saunders Kevin O KO Fera Daniela D Kwong Peter D PD Seder Robert A RA Bartesaghi Alberto A Shaw George M GM Acharya Priyamvada P Haynes Barton F BF

Cell 20210520 11

Natural antibodies (Abs) can target host glycans on the surface of pathogens. We studied the evolution of glycan-reactive B cells of rhesus macaques and humans using glycosylated HIV-1 envelope (Env) as a model antigen. 2G12 is a broadly neutralizing Ab (bnAb) that targets a conserved glycan patch on Env of geographically diverse HIV-1 strains using a unique heavy-chain (V<sub>H</sub>) domain-swapped architecture that results in fragment antigen-binding (Fab) dimerization. Here, we describe HIV- ...[more]

PMID: 34019795

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Project description:Gut commensal bacteria are known to have a significant role in regulating the innate and adaptive immune homeostasis. Alterations in the intestinal microbial composition have been associated with several disease states, including autoimmune and inflammatory conditions. However, it is not entirely clear how commensal gut microbiota modulate and contribute to the systemic immunity, and whether circulating elements of the host immune system could regulate the microbiome. Thus, we have studied the diversity and abundance of specific taxons in the gut microbiota of inbred GalT-KO mice during 7 months of animal life by metagenetic high-throughput sequencing (16S rRNA gene, variable regions V3-V5). The repertoire of glycan-specific natural antibodies, obtained by printed glycan array technology, was then associated with the microbial diversity for each animal by metagenome-wide association studies (MWAS). Our data show that the orders clostridiales (most abundant), bacteriodales, lactobacillales, and deferribacterales may be associated with the development of the final repertoire of natural anti-glycan antibodies in GalT-KO mice. The main changes in microbiota diversity (month-2 and month-3) were related to important changes in levels and repertoire of natural anti-glycan antibodies in these mice. Additionally, significant positive and negative associations were found between the gut microbiota and the pattern of specific anti-glycan antibodies. Regarding individual features, the gut microbiota and the corresponding repertoire of natural anti-glycan antibodies showed differences among the examined animals. We also found redundancy in different taxa associated with the development of specific anti-glycan antibodies. Differences in microbial diversity did not, therefore, necessarily influence the overall functional output of the gut microbiome of GalT-KO mice. In summary, the repertoire of natural anti-carbohydrate antibodies may be partially determined by the continuous antigenic stimulation produced by the gut bacterial population of each GalT-KO mouse. Small differences in gut microbiota diversity could determine different repertoire and levels of natural anti-glycan antibodies and consequently might induce different immune responses to pathogens or other potential threats.

Dataset Information

Fab-dimerized glycan-reactive antibodies are a structural category of natural antibodies.

Publications

Fab-dimerized glycan-reactive antibodies are a structural category of natural antibodies.

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