Aye, RachealSutton, HarryNduati, Eunice W.Kai, OscarMwacharo, JedidaMusyoki, JenniferOtieno, EdwardWambua, JulianaBejon, PhilipCockburn, IanNdungu, Francis M.2022-09-292022-09-290014-2980http://hdl.handle.net/1885/274191Atypical 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.This work was supported by start-up funds from the Australian National University to IAC and NHMRC project grant support to IAC (GNT1158404). FMN was supported by an MRC/DFID African Research Leadership Award (MR/P020321/1), a Senior Fellowship from EDCTP (TMA2016SF-1513) and the samples were collected within the Kilifi immunology cohorts supported by various Wellcome grants over the years. RA was supported through the DELTAS Africa Initiative (DEL-15-003). The DELTAS Africa Initiative is an independent funding scheme of the African Academy of Sciences' (AAS) Alliance for Accelerating Excellence in Science in Africa (AESA) and supported by the New Partnership for Africa's Development Planning and Coordinating Agency (NEPAD Agency) with funding from the Wellcome Trust (107769/Z/10/Z) and the UK government.application/pdfen-AU© 2020 The Authorshttps://creativecommons.org/licenses/by/4.0/B-cell memoryimmunological memorymalariaPlasmodiumtetanus toxoid2020-03-2910.1002/eji.2019484732021-11-28Creative Commons Attribution License