Pregnancy-induced effects on memory B-cell development in multiple sclerosis

Abstract In MS, pathogenic memory B cells infiltrate the brain and develop into antibody-secreting cells. Chemokine receptors not only define their brain-infiltrating capacity, but also assist in their maturation in germinal centers. How this corresponds to pregnancy, as a naturally occurring modifi...

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Autores principales:	Malou Janssen, Liza Rijvers, Steven C. Koetzier, Annet F. Wierenga-Wolf, Marie-José Melief, Jamie van Langelaar, Tessel F. Runia, Christianne J. M. de Groot, Rinze Neuteboom, Joost Smolders, Marvin M. van Luijn
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/32ebd22e76a44d9db5b13828cd756796
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spelling	oai:doaj.org-article:32ebd22e76a44d9db5b13828cd7567962021-12-02T14:59:29ZPregnancy-induced effects on memory B-cell development in multiple sclerosis10.1038/s41598-021-91655-92045-2322https://doaj.org/article/32ebd22e76a44d9db5b13828cd7567962021-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-91655-9https://doaj.org/toc/2045-2322Abstract In MS, pathogenic memory B cells infiltrate the brain and develop into antibody-secreting cells. Chemokine receptors not only define their brain-infiltrating capacity, but also assist in their maturation in germinal centers. How this corresponds to pregnancy, as a naturally occurring modifier of MS, is underexplored. Here, we aimed to study the impact of pregnancy on both ex vivo and in vitro B-cell differentiation in MS. The composition and outgrowth of peripheral B cells were compared between 19 MS pregnant patients and 12 healthy controls during the third trimester of pregnancy (low relapse risk) and postpartum (high relapse risk). Transitional, and not naive mature, B-cell frequencies were found to drop in the third trimester, which was most prominent in patients who experienced a pre-pregnancy relapse. Early after delivery, these frequencies raised again, while memory B -cell frequencies modestly declined. CXCR4 was downregulated and CXCR5, CXCR3 and CCR6 were upregulated on postpartum memory B cells, implying enhanced recruitment into germinal center light zones for interaction with T follicular helper (TFH) cells. Postpartum memory B cells of MS patients expressed higher levels of CCR6 and preferentially developed into plasma cells under TFH-like in vitro conditions. These findings imply that memory B- cell differentiation contributes to postpartum relapse risk in MS.Malou JanssenLiza RijversSteven C. KoetzierAnnet F. Wierenga-WolfMarie-José MeliefJamie van LangelaarTessel F. RuniaChristianne J. M. de GrootRinze NeuteboomJoost SmoldersMarvin M. van LuijnNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-8 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Malou Janssen Liza Rijvers Steven C. Koetzier Annet F. Wierenga-Wolf Marie-José Melief Jamie van Langelaar Tessel F. Runia Christianne J. M. de Groot Rinze Neuteboom Joost Smolders Marvin M. van Luijn Pregnancy-induced effects on memory B-cell development in multiple sclerosis
description	Abstract In MS, pathogenic memory B cells infiltrate the brain and develop into antibody-secreting cells. Chemokine receptors not only define their brain-infiltrating capacity, but also assist in their maturation in germinal centers. How this corresponds to pregnancy, as a naturally occurring modifier of MS, is underexplored. Here, we aimed to study the impact of pregnancy on both ex vivo and in vitro B-cell differentiation in MS. The composition and outgrowth of peripheral B cells were compared between 19 MS pregnant patients and 12 healthy controls during the third trimester of pregnancy (low relapse risk) and postpartum (high relapse risk). Transitional, and not naive mature, B-cell frequencies were found to drop in the third trimester, which was most prominent in patients who experienced a pre-pregnancy relapse. Early after delivery, these frequencies raised again, while memory B -cell frequencies modestly declined. CXCR4 was downregulated and CXCR5, CXCR3 and CCR6 were upregulated on postpartum memory B cells, implying enhanced recruitment into germinal center light zones for interaction with T follicular helper (TFH) cells. Postpartum memory B cells of MS patients expressed higher levels of CCR6 and preferentially developed into plasma cells under TFH-like in vitro conditions. These findings imply that memory B- cell differentiation contributes to postpartum relapse risk in MS.
format	article
author	Malou Janssen Liza Rijvers Steven C. Koetzier Annet F. Wierenga-Wolf Marie-José Melief Jamie van Langelaar Tessel F. Runia Christianne J. M. de Groot Rinze Neuteboom Joost Smolders Marvin M. van Luijn
author_facet	Malou Janssen Liza Rijvers Steven C. Koetzier Annet F. Wierenga-Wolf Marie-José Melief Jamie van Langelaar Tessel F. Runia Christianne J. M. de Groot Rinze Neuteboom Joost Smolders Marvin M. van Luijn
author_sort	Malou Janssen
title	Pregnancy-induced effects on memory B-cell development in multiple sclerosis
title_short	Pregnancy-induced effects on memory B-cell development in multiple sclerosis
title_full	Pregnancy-induced effects on memory B-cell development in multiple sclerosis
title_fullStr	Pregnancy-induced effects on memory B-cell development in multiple sclerosis
title_full_unstemmed	Pregnancy-induced effects on memory B-cell development in multiple sclerosis
title_sort	pregnancy-induced effects on memory b-cell development in multiple sclerosis
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/32ebd22e76a44d9db5b13828cd756796
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Pregnancy-induced effects on memory B-cell development in multiple sclerosis

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