Malaria exposure drives both cognate and bystander human B cells to adopt an atypical phenotype

Atypical memory B cells (aMBCs) are found in elevated numbers in individuals exposed to malaria. A key question is whether malaria induces aMBCs as a result of exposure to Ag, or non-Ag-specific mechanisms. We identified Plasmodium and bystander tetanus toxoid (TT) specific B cells in individuals fr...

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Главные авторы: Aye, R, Sutton, HJ, Nduati, EW, Kai, O, Mwacharo, J, Musyoki, J, Otieno, E, Wambua, J, Bejon, P, Cockburn, IA, Ndungu, FM
Формат: Journal article
Язык:English
Опубликовано: Wiley 2020
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author Aye, R
Sutton, HJ
Nduati, EW
Kai, O
Mwacharo, J
Musyoki, J
Otieno, E
Wambua, J
Bejon, P
Cockburn, IA
Ndungu, FM
author_facet Aye, R
Sutton, HJ
Nduati, EW
Kai, O
Mwacharo, J
Musyoki, J
Otieno, E
Wambua, J
Bejon, P
Cockburn, IA
Ndungu, FM
author_sort Aye, R
collection OXFORD
description Atypical memory B cells (aMBCs) are found in elevated numbers in individuals exposed to malaria. A key question is whether malaria induces aMBCs as a result of exposure to Ag, or non-Ag-specific mechanisms. We identified Plasmodium and bystander tetanus toxoid (TT) specific B cells in individuals from areas of previous and persistent exposure to malaria using tetramers. Malaria-specific B cells were more likely to be aMBCs than TT-specific B cells. However, TT-specific B cells from individuals with continuous exposure to malaria were more likely to be aMBCs than TT-specific B cells in individuals from areas where transmission has ceased. Finally, sequences of BCRs specific for a blood stage malaria-Ag were more highly mutated than sequences from TT-specific BCRs and under strong negative selection, indicative of ongoing antigenic pressure. Our data suggest both persistent Ag exposure and the inflammatory environment shape the B-cell response to malaria and bystander Ags.
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spelling oxford-uuid:d2db813c-778a-4e90-b3cf-0ca7d5fa7ff42022-03-27T08:07:13ZMalaria exposure drives both cognate and bystander human B cells to adopt an atypical phenotypeJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:d2db813c-778a-4e90-b3cf-0ca7d5fa7ff4EnglishSymplectic ElementsWiley2020Aye, RSutton, HJNduati, EWKai, OMwacharo, JMusyoki, JOtieno, EWambua, JBejon, PCockburn, IANdungu, FMAtypical memory B cells (aMBCs) are found in elevated numbers in individuals exposed to malaria. A key question is whether malaria induces aMBCs as a result of exposure to Ag, or non-Ag-specific mechanisms. We identified Plasmodium and bystander tetanus toxoid (TT) specific B cells in individuals from areas of previous and persistent exposure to malaria using tetramers. Malaria-specific B cells were more likely to be aMBCs than TT-specific B cells. However, TT-specific B cells from individuals with continuous exposure to malaria were more likely to be aMBCs than TT-specific B cells in individuals from areas where transmission has ceased. Finally, sequences of BCRs specific for a blood stage malaria-Ag were more highly mutated than sequences from TT-specific BCRs and under strong negative selection, indicative of ongoing antigenic pressure. Our data suggest both persistent Ag exposure and the inflammatory environment shape the B-cell response to malaria and bystander Ags.
spellingShingle Aye, R
Sutton, HJ
Nduati, EW
Kai, O
Mwacharo, J
Musyoki, J
Otieno, E
Wambua, J
Bejon, P
Cockburn, IA
Ndungu, FM
Malaria exposure drives both cognate and bystander human B cells to adopt an atypical phenotype
title Malaria exposure drives both cognate and bystander human B cells to adopt an atypical phenotype
title_full Malaria exposure drives both cognate and bystander human B cells to adopt an atypical phenotype
title_fullStr Malaria exposure drives both cognate and bystander human B cells to adopt an atypical phenotype
title_full_unstemmed Malaria exposure drives both cognate and bystander human B cells to adopt an atypical phenotype
title_short Malaria exposure drives both cognate and bystander human B cells to adopt an atypical phenotype
title_sort malaria exposure drives both cognate and bystander human b cells to adopt an atypical phenotype
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