Longitudinal Dynamics of Human B-Cell Response at the Single-Cell Level in Response to Tdap Vaccination

To mount an adequate immune response against pathogens, stepwise mutation and selection processes are crucial functions of the adaptive immune system. To better characterize a successful vaccination response, we performed longitudinal (days 0, 5, 7, 10, and 14 after Boostrix vaccination) analysis of...

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Autores principales:	Indu Khatri, Annieck M. Diks, Erik B. van den Akker, Liesbeth E. M. Oosten, Jaap Jan Zwaginga, Marcel J. T. Reinders, Jacques J. M. van Dongen, Magdalena A. Berkowska
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	B-cell receptor repertoire Tdap vaccine pertussis single cell vaccination Medicine R
Acceso en línea:	https://doaj.org/article/b0c17f6865ea4e8abfba54d247b6d7f6
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spelling	oai:doaj.org-article:b0c17f6865ea4e8abfba54d247b6d7f62021-11-25T19:11:33ZLongitudinal Dynamics of Human B-Cell Response at the Single-Cell Level in Response to Tdap Vaccination10.3390/vaccines91113522076-393Xhttps://doaj.org/article/b0c17f6865ea4e8abfba54d247b6d7f62021-11-01T00:00:00Zhttps://www.mdpi.com/2076-393X/9/11/1352https://doaj.org/toc/2076-393XTo mount an adequate immune response against pathogens, stepwise mutation and selection processes are crucial functions of the adaptive immune system. To better characterize a successful vaccination response, we performed longitudinal (days 0, 5, 7, 10, and 14 after Boostrix vaccination) analysis of the single-cell transcriptome as well as the B-cell receptor (BCR) repertoire (scBCR-rep) in plasma cells of an immunized donor and compared it with baseline B-cell characteristics as well as flow cytometry findings. Based on the flow cytometry knowledge and literature findings, we discriminated individual B-cell subsets in the transcriptomics data and traced over-time maturation of plasmablasts/plasma cells (PB/PCs) and identified the pathways associated with the plasma cell maturation. We observed that the repertoire in PB/PCs differed from the baseline B-cell repertoire e.g., regarding expansion of unique clones in post-vaccination visits, high usage of IGHG1 in expanded clones, increased class-switching events post-vaccination represented by clonotypes spanning multiple IGHC classes and positive selection of CDR3 sequences over time. Importantly, the Variable gene family-based clustering of BCRs represented a similar measure as the gene-based clustering, but certainly improved the clustering of BCRs, as BCRs from duplicated Variable gene families could be clustered together. Finally, we developed a query tool to dissect the immune response to the components of the Boostrix vaccine. Using this tool, we could identify the BCRs related to anti-tetanus and anti-pertussis toxoid BCRs. Collectively, we developed a bioinformatic workflow which allows description of the key features of an ongoing (longitudinal) immune response, such as activation of PB/PCs, Ig class switching, somatic hypermutation, and clonal expansion, all of which are hallmarks of antigen exposure, followed by mutation & selection processes.Indu KhatriAnnieck M. DiksErik B. van den AkkerLiesbeth E. M. OostenJaap Jan ZwagingaMarcel J. T. ReindersJacques J. M. van DongenMagdalena A. BerkowskaMDPI AGarticleB-cell receptor repertoireTdap vaccinepertussissingle cellvaccinationMedicineRENVaccines, Vol 9, Iss 1352, p 1352 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	B-cell receptor repertoire Tdap vaccine pertussis single cell vaccination Medicine R
spellingShingle	B-cell receptor repertoire Tdap vaccine pertussis single cell vaccination Medicine R Indu Khatri Annieck M. Diks Erik B. van den Akker Liesbeth E. M. Oosten Jaap Jan Zwaginga Marcel J. T. Reinders Jacques J. M. van Dongen Magdalena A. Berkowska Longitudinal Dynamics of Human B-Cell Response at the Single-Cell Level in Response to Tdap Vaccination
description	To mount an adequate immune response against pathogens, stepwise mutation and selection processes are crucial functions of the adaptive immune system. To better characterize a successful vaccination response, we performed longitudinal (days 0, 5, 7, 10, and 14 after Boostrix vaccination) analysis of the single-cell transcriptome as well as the B-cell receptor (BCR) repertoire (scBCR-rep) in plasma cells of an immunized donor and compared it with baseline B-cell characteristics as well as flow cytometry findings. Based on the flow cytometry knowledge and literature findings, we discriminated individual B-cell subsets in the transcriptomics data and traced over-time maturation of plasmablasts/plasma cells (PB/PCs) and identified the pathways associated with the plasma cell maturation. We observed that the repertoire in PB/PCs differed from the baseline B-cell repertoire e.g., regarding expansion of unique clones in post-vaccination visits, high usage of IGHG1 in expanded clones, increased class-switching events post-vaccination represented by clonotypes spanning multiple IGHC classes and positive selection of CDR3 sequences over time. Importantly, the Variable gene family-based clustering of BCRs represented a similar measure as the gene-based clustering, but certainly improved the clustering of BCRs, as BCRs from duplicated Variable gene families could be clustered together. Finally, we developed a query tool to dissect the immune response to the components of the Boostrix vaccine. Using this tool, we could identify the BCRs related to anti-tetanus and anti-pertussis toxoid BCRs. Collectively, we developed a bioinformatic workflow which allows description of the key features of an ongoing (longitudinal) immune response, such as activation of PB/PCs, Ig class switching, somatic hypermutation, and clonal expansion, all of which are hallmarks of antigen exposure, followed by mutation & selection processes.
format	article
author	Indu Khatri Annieck M. Diks Erik B. van den Akker Liesbeth E. M. Oosten Jaap Jan Zwaginga Marcel J. T. Reinders Jacques J. M. van Dongen Magdalena A. Berkowska
author_facet	Indu Khatri Annieck M. Diks Erik B. van den Akker Liesbeth E. M. Oosten Jaap Jan Zwaginga Marcel J. T. Reinders Jacques J. M. van Dongen Magdalena A. Berkowska
author_sort	Indu Khatri
title	Longitudinal Dynamics of Human B-Cell Response at the Single-Cell Level in Response to Tdap Vaccination
title_short	Longitudinal Dynamics of Human B-Cell Response at the Single-Cell Level in Response to Tdap Vaccination
title_full	Longitudinal Dynamics of Human B-Cell Response at the Single-Cell Level in Response to Tdap Vaccination
title_fullStr	Longitudinal Dynamics of Human B-Cell Response at the Single-Cell Level in Response to Tdap Vaccination
title_full_unstemmed	Longitudinal Dynamics of Human B-Cell Response at the Single-Cell Level in Response to Tdap Vaccination
title_sort	longitudinal dynamics of human b-cell response at the single-cell level in response to tdap vaccination
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/b0c17f6865ea4e8abfba54d247b6d7f6
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Longitudinal Dynamics of Human B-Cell Response at the Single-Cell Level in Response to Tdap Vaccination

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