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

Racheal Aye, Henry J Sutton, Eunice W Nduati, Oscar Kai, Jedida Mwacharo, Jennifer Musyoki, Edward Otieno, Juliana Wambua, Philip Bejon, Ian A Cockburn, Francis M Ndungu

European journal of immunology 2020 Aug

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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. © 2020 The Authors. European Journal of Immunology published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Citation

Racheal Aye, Henry J Sutton, Eunice W Nduati, Oscar Kai, Jedida Mwacharo, Jennifer Musyoki, Edward Otieno, Juliana Wambua, Philip Bejon, Ian A Cockburn, Francis M Ndungu. Malaria exposure drives both cognate and bystander human B cells to adopt an atypical phenotype. European journal of immunology. 2020 Aug;50(8):1187-1194