A cluster of broadly neutralizing IgG against BK polyomavirus in a repertoire dominated by IgM

The BK polyomavirus (BKPyV) is an opportunistic pathogen, which is only pathogenic in immunosuppressed individuals, such as kidney transplant recipients, in whom BKPyV can cause significant morbidity. To identify broadly neutralizing antibodies against this virus, we used fluorescence-labeled BKPyV...

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Published in:Life science alliance 2023-04, Vol.6 (4), p.e202201567
Main Authors: Nguyen, Ngoc-Khanh, Devilder, Marie-Claire, Gautreau-Rolland, Laetitia, Fourgeux, Cynthia, Sinha, Debajyoti, Poschmann, Jeremie, Hourmant, Maryvonne, Bressollette-Bodin, Céline, Saulquin, Xavier, McIlroy, Dorian
Format: Article
Language:English
Subjects:
Adaptive immunology
BK Virus - genetics
Human health and pathology
Humans
Immunoglobulin G
Immunoglobulin M
Immunology
Infectious diseases
Kidney Transplantation - adverse effects
Leukocytes, Mononuclear
Life Sciences
Microbiology and Parasitology
Polyomavirus Infections - etiology
Urology and Nephrology
Virology
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Summary:The BK polyomavirus (BKPyV) is an opportunistic pathogen, which is only pathogenic in immunosuppressed individuals, such as kidney transplant recipients, in whom BKPyV can cause significant morbidity. To identify broadly neutralizing antibodies against this virus, we used fluorescence-labeled BKPyV virus-like particles to sort BKPyV-specific B cells from the PBMC of KTx recipients, then single-cell RNAseq to obtain paired heavy- and light-chain antibody sequences from 2,106 sorted B cells. The BKPyV-specific repertoire was highly diverse in terms of both V-gene usage and clonotype diversity and included most of the IgM B cells, including many with extensive somatic hypermutation. In two patients where sufficient data were available, IgM B cells in the BKPyV-specific dataset had significant differences in V-gene usage compared with IgG B cells from the same patient. CDR3 sequence-based clustering allowed us to identify and characterize three broadly neutralizing "41F17-like" clonotypes that were predominantly IgG, suggesting that some specific BKPyV capsid epitopes are preferentially targeted by IgG.
ISSN:2575-1077
2575-1077
DOI:10.26508/lsa.202201567