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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ftdoajarticles:oai:doaj.org/article:7854bd5a269c4627924f579267bd1b30 2023-05-15T15:14:43+02:00 Longitudinal analysis of FcRL5 expression and clonal relationships among classical and atypical memory B cells following malaria S. Jake Gonzales Sebastiaan Bol Ashley E. Braddom Richard Sullivan Raphael A. Reyes Isaac Ssewanyana Erica Eggers Bryan Greenhouse Evelien M. Bunnik 2021-11-01T00:00:00Z https://doi.org/10.1186/s12936-021-03970-1 https://doaj.org/article/7854bd5a269c4627924f579267bd1b30 EN eng BMC https://doi.org/10.1186/s12936-021-03970-1 https://doaj.org/toc/1475-2875 doi:10.1186/s12936-021-03970-1 1475-2875 https://doaj.org/article/7854bd5a269c4627924f579267bd1b30 Malaria Journal, Vol 20, Iss 1, Pp 1-15 (2021) 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 article 2021 ftdoajarticles https://doi.org/10.1186/s12936-021-03970-1 2022-12-31T09:16:41Z 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. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic Malaria Journal 20 1 |
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Directory of Open Access Journals: DOAJ Articles |
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ftdoajarticles |
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English |
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 |
topic_facet |
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 |
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 in Journal/Newspaper |
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://doi.org/10.1186/s12936-021-03970-1 https://doaj.org/article/7854bd5a269c4627924f579267bd1b30 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
Malaria Journal, Vol 20, Iss 1, Pp 1-15 (2021) |
op_relation |
https://doi.org/10.1186/s12936-021-03970-1 https://doaj.org/toc/1475-2875 doi:10.1186/s12936-021-03970-1 1475-2875 https://doaj.org/article/7854bd5a269c4627924f579267bd1b30 |
op_doi |
https://doi.org/10.1186/s12936-021-03970-1 |
container_title |
Malaria Journal |
container_volume |
20 |
container_issue |
1 |
_version_ |
1766345133455835136 |