Longitudinal analysis of FcRL5 expression and clonal relationships among classical and atypical memory B cells following malaria

Abstract Background Chronic and frequently recurring infectious diseases, such as malaria, are associated with expanded populations of atypical memory B cells (MBCs). These cells are different from classical MBCs by the lack of surface markers CD21 and CD27 and increased expression of inhibitory rec...

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Autores principales:	S. Jake Gonzales, Sebastiaan Bol, Ashley E. Braddom, Richard Sullivan, Raphael A. Reyes, Isaac Ssewanyana, Erica Eggers, Bryan Greenhouse, Evelien M. Bunnik
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	Plasmodium falciparum Adaptive immune response Humoral immunity B cell differentiation Infection BCR-sequencing Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216
Acceso en línea:	https://doaj.org/article/7854bd5a269c4627924f579267bd1b30
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spelling	oai:doaj.org-article:7854bd5a269c4627924f579267bd1b302021-11-14T12:33:49ZLongitudinal analysis of FcRL5 expression and clonal relationships among classical and atypical memory B cells following malaria10.1186/s12936-021-03970-11475-2875https://doaj.org/article/7854bd5a269c4627924f579267bd1b302021-11-01T00:00:00Zhttps://doi.org/10.1186/s12936-021-03970-1https://doaj.org/toc/1475-2875Abstract Background Chronic and frequently recurring infectious diseases, such as malaria, are associated with expanded populations of atypical memory B cells (MBCs). These cells are different from classical MBCs by the lack of surface markers CD21 and CD27 and increased expression of inhibitory receptors, such as FcRL5. While the phenotype and conditions leading to neogenesis of atypical MBCs in malaria-experienced individuals have been studied extensively, the origin of these cells remains equivocal. Functional similarities between FcRL5+ atypical MBCs and FcRL5+ classical MBCs have been reported, suggesting that these cells may be developmentally related. Methods Here, a longitudinal analysis of FcRL5 expression in various B cell subsets was performed in two children from a high transmission region in Uganda over a 6-month period in which both children experienced a malaria episode. Using B-cell receptor (BCR)-sequencing to track clonally related cells, the connections between IgM+ and IgG+ atypical MBCs and other B cell subsets were studied. Results The highest expression of FcRL5 was found among IgG+ atypical MBCs, but FcRL5+ cells were present in all MBC subsets. Following malaria, FcRL5 expression increased in all IgM+ MBC subsets analysed here: classical, activated, and atypical MBCs, while results for IgG+ MBC subsets were inconclusive. IgM+ atypical MBCs showed few connections with other B cell subsets, higher turnover than IgG+ atypical MBCs, and were predominantly derived from naïve B cells and FcRL5− IgM+ classical MBCs. In contrast, IgG+ atypical MBCs were clonally expanded and connected with classical MBCs. IgG+ atypical MBCs present after a malaria episode mainly originated from FcRL5+ IgG+ classical MBCs. Conclusions Collectively, these results suggest fundamental differences between unswitched and class-switched B cell populations and provide clues about the primary developmental pathways of atypical MBCs in malaria-experienced individuals.S. Jake GonzalesSebastiaan BolAshley E. BraddomRichard SullivanRaphael A. ReyesIsaac SsewanyanaErica EggersBryan GreenhouseEvelien M. BunnikBMCarticlePlasmodium falciparumAdaptive immune responseHumoral immunityB cell differentiationInfectionBCR-sequencingArctic medicine. Tropical medicineRC955-962Infectious and parasitic diseasesRC109-216ENMalaria Journal, Vol 20, Iss 1, Pp 1-15 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Plasmodium falciparum Adaptive immune response Humoral immunity B cell differentiation Infection BCR-sequencing Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216
spellingShingle	Plasmodium falciparum Adaptive immune response Humoral immunity B cell differentiation Infection BCR-sequencing Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 S. Jake Gonzales Sebastiaan Bol Ashley E. Braddom Richard Sullivan Raphael A. Reyes Isaac Ssewanyana Erica Eggers Bryan Greenhouse Evelien M. Bunnik Longitudinal analysis of FcRL5 expression and clonal relationships among classical and atypical memory B cells following malaria
description	Abstract Background Chronic and frequently recurring infectious diseases, such as malaria, are associated with expanded populations of atypical memory B cells (MBCs). These cells are different from classical MBCs by the lack of surface markers CD21 and CD27 and increased expression of inhibitory receptors, such as FcRL5. While the phenotype and conditions leading to neogenesis of atypical MBCs in malaria-experienced individuals have been studied extensively, the origin of these cells remains equivocal. Functional similarities between FcRL5+ atypical MBCs and FcRL5+ classical MBCs have been reported, suggesting that these cells may be developmentally related. Methods Here, a longitudinal analysis of FcRL5 expression in various B cell subsets was performed in two children from a high transmission region in Uganda over a 6-month period in which both children experienced a malaria episode. Using B-cell receptor (BCR)-sequencing to track clonally related cells, the connections between IgM+ and IgG+ atypical MBCs and other B cell subsets were studied. Results The highest expression of FcRL5 was found among IgG+ atypical MBCs, but FcRL5+ cells were present in all MBC subsets. Following malaria, FcRL5 expression increased in all IgM+ MBC subsets analysed here: classical, activated, and atypical MBCs, while results for IgG+ MBC subsets were inconclusive. IgM+ atypical MBCs showed few connections with other B cell subsets, higher turnover than IgG+ atypical MBCs, and were predominantly derived from naïve B cells and FcRL5− IgM+ classical MBCs. In contrast, IgG+ atypical MBCs were clonally expanded and connected with classical MBCs. IgG+ atypical MBCs present after a malaria episode mainly originated from FcRL5+ IgG+ classical MBCs. Conclusions Collectively, these results suggest fundamental differences between unswitched and class-switched B cell populations and provide clues about the primary developmental pathways of atypical MBCs in malaria-experienced individuals.
format	article
author	S. Jake Gonzales Sebastiaan Bol Ashley E. Braddom Richard Sullivan Raphael A. Reyes Isaac Ssewanyana Erica Eggers Bryan Greenhouse Evelien M. Bunnik
author_facet	S. Jake Gonzales Sebastiaan Bol Ashley E. Braddom Richard Sullivan Raphael A. Reyes Isaac Ssewanyana Erica Eggers Bryan Greenhouse Evelien M. Bunnik
author_sort	S. Jake Gonzales
title	Longitudinal analysis of FcRL5 expression and clonal relationships among classical and atypical memory B cells following malaria
title_short	Longitudinal analysis of FcRL5 expression and clonal relationships among classical and atypical memory B cells following malaria
title_full	Longitudinal analysis of FcRL5 expression and clonal relationships among classical and atypical memory B cells following malaria
title_fullStr	Longitudinal analysis of FcRL5 expression and clonal relationships among classical and atypical memory B cells following malaria
title_full_unstemmed	Longitudinal analysis of FcRL5 expression and clonal relationships among classical and atypical memory B cells following malaria
title_sort	longitudinal analysis of fcrl5 expression and clonal relationships among classical and atypical memory b cells following malaria
publisher	BMC
publishDate	2021
url	https://doaj.org/article/7854bd5a269c4627924f579267bd1b30
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Longitudinal analysis of FcRL5 expression and clonal relationships among classical and atypical memory B cells following malaria

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