Abstract
Plasmodium falciparum infections elicit strong humoral immune responses to two main groups of antigens expressed by blood-stage parasites: merozoite antigens that are involved in the erythrocyte invasion process and variant surface antigens that mediate endothelial sequestration of infected erythrocytes. Long-lived B cells against both antigen classes can be detected in the circulation for years after exposure, but have not been directly compared. Here, we studied the phenotype of long-lived memory and atypical B cells to merozoite antigens (MSP1 and AMA1) and variant surface antigens (the CIDRα1 domain of PfEMP1) in ten Ugandan adults before and after local reduction of P. falciparum transmission. After a median of 1.7 years without P. falciparum infections, the percentage of antigen-specific activated B cells declined, but long-lived antigen-specific B cells were still detectable in all individuals. The majority of MSP1/AMA1-specific B cells were CD95+CD11c+ memory B cells, which are primed for rapid differentiation into antibody-secreting cells, and FcRL5-Tbet- atypical B cells. On the other hand, most CIDRα1-specific B cells were CD95-CD11cmemory B cells. CIDRα1-specific B cells were also enriched among a subset of atypical B cells that seem poised for antigen presentation. These results point to differences in how these antigens are recognized or processed by the immune system and how P. falciparum-specific B cells will respond upon re-infection.
| Originalsprog | Engelsk |
|---|---|
| Artikelnummer | e1012661 |
| Tidsskrift | PLoS Pathogens |
| Vol/bind | 20 |
| Udgave nummer | 10 |
| Antal sider | 22 |
| ISSN | 1553-7366 |
| DOI | |
| Status | Udgivet - 2024 |
Bibliografisk note
Funding Information:This work was supported by the National Institutes of Health (R01 AI153425 to EMB, F31 AI169993 to RAR, TL1 TR002647 to RAR, U19 AI150741 to BG and PJ, and U19 AI089674 that funds the PRISM cohort). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Plasmids encoding 3D7 MSP1-bio, AMA1-bio, and BirA, were a kind gift from Dr. Gavin Wright (Wellcome Sanger Institute). Data were generated in the Flow Cytometry Shared Resource at UT Health San Antonio, which is supported by a grant from the National Cancer Institute (P30 CA054174) to the Mays Cancer Center, a grant from the Cancer Prevention and Research Institute of Texas (CPRIT) (RP210126), a grant from the National Institutes of Health (S10 OD030432), and support from the Office of the Vice President for Research at UT Health San Antonio.
Publisher Copyright:
© 2024 Reyes et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.