Differences in Phenotype Between Long-lived Memory B Cells Against Plasmodium Falciparum Merozoite Antigens and Variant Surface Antigens

Overview

Journal PLoS Pathog

Specialty Microbiology

Date 2024 Oct 28

PMID 39466842

Authors

Raphael A Reyes

Louise Turner

Isaac Ssewanyana

Prasanna Jagannathan

Margaret E Feeney

Thomas Lavstsen

Bryan Greenhouse

Sebastiaan Bol

Evelien M Bunnik

Affiliations

Soon will be listed here.

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-T-bet- atypical B cells. On the other hand, most CIDRα1-specific B cells were CD95-CD11c- memory 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.

References

Jahnmatz P, Sundling C, Yman V, Widman L, Asghar M, Sonden K . Memory B-Cell Responses Against Merozoite Antigens After Acute Malaria, Assessed Over One Year Using a Novel Multiplexed FluoroSpot Assay. Front Immunol. 2021; 11:619398. PMC: 7928423. DOI: 10.3389/fimmu.2020.619398. View

Reyes R, Clarke K, Gonzales S, Cantwell A, Garza R, Catano G . SARS-CoV-2 spike-specific memory B cells express higher levels of T-bet and FcRL5 after non-severe COVID-19 as compared to severe disease. PLoS One. 2021; 16(12):e0261656. PMC: 8694470. DOI: 10.1371/journal.pone.0261656. View

Gao X, Shen Q, Roco J, Dalton B, Frith K, Munier C . Zeb2 drives the formation of CD11c atypical B cells to sustain germinal centers that control persistent infection. Sci Immunol. 2024; 9(93):eadj4748. DOI: 10.1126/sciimmunol.adj4748. View

Portugal S, Tipton C, Sohn H, Kone Y, Wang J, Li S . Malaria-associated atypical memory B cells exhibit markedly reduced B cell receptor signaling and effector function. Elife. 2015; 4. PMC: 4444601. DOI: 10.7554/eLife.07218. View

Rivera-Correa J, Mackroth M, Jacobs T, Schulze Zur Wiesch J, Rolling T, Rodriguez A . Atypical memory B-cells are associated with anemia through anti-phosphatidylserine antibodies. Elife. 2019; 8. PMC: 6853636. DOI: 10.7554/eLife.48309. View

Crompton P, Kayala M, Traore B, Kayentao K, Ongoiba A, Weiss G . A prospective analysis of the Ab response to Plasmodium falciparum before and after a malaria season by protein microarray. Proc Natl Acad Sci U S A. 2010; 107(15):6958-63. PMC: 2872454. DOI: 10.1073/pnas.1001323107. View

Braddom A, Bol S, Gonzales S, Reyes R, Musinguzi K, Nankya F . B Cell Receptor Repertoire Analysis in Malaria-Naive and Malaria-Experienced Individuals Reveals Unique Characteristics of Atypical Memory B Cells. mSphere. 2021; 6(5):e0072621. PMC: 8550134. DOI: 10.1128/mSphere.00726-21. View

Ayieko C, Maue A, Jura W, Noland G, Ayodo G, Rochford R . Changes in B Cell Populations and Merozoite Surface Protein-1-Specific Memory B Cell Responses after Prolonged Absence of Detectable P. falciparum Infection. PLoS One. 2013; 8(6):e67230. PMC: 3695086. DOI: 10.1371/journal.pone.0067230. View

Jahnmatz P, Nyabundi D, Sundling C, Widman L, Mwacharo J, Musyoki J . -Specific Memory B-Cell and Antibody Responses Are Associated With Immunity in Children Living in an Endemic Area of Kenya. Front Immunol. 2022; 13:799306. PMC: 8959630. DOI: 10.3389/fimmu.2022.799306. View

10.

Daniel P, Krammer P . Activation induces sensitivity toward APO-1 (CD95)-mediated apoptosis in human B cells. J Immunol. 1994; 152(12):5624-32. View

11.

Crotty S, Felgner P, Davies H, Glidewell J, Villarreal L, Ahmed R . Cutting edge: long-term B cell memory in humans after smallpox vaccination. J Immunol. 2003; 171(10):4969-73. DOI: 10.4049/jimmunol.171.10.4969. View

12.

Hong S, Zhang Z, Liu H, Tian M, Zhu X, Zhang Z . B Cells Are the Dominant Antigen-Presenting Cells that Activate Naive CD4 T Cells upon Immunization with a Virus-Derived Nanoparticle Antigen. Immunity. 2018; 49(4):695-708.e4. DOI: 10.1016/j.immuni.2018.08.012. View

13.

Arroyo E, Pepper M . B cells are sufficient to prime the dominant CD4+ Tfh response to Plasmodium infection. J Exp Med. 2019; 217(2). PMC: 7041722. DOI: 10.1084/jem.20190849. View

14.

Batista F, Harwood N . The who, how and where of antigen presentation to B cells. Nat Rev Immunol. 2008; 9(1):15-27. DOI: 10.1038/nri2454. View

15.

Ambegaonkar A, Holla P, Dizon B, Sohn H, Pierce S . Atypical B cells in chronic infectious diseases and systemic autoimmunity: puzzles with many missing pieces. Curr Opin Immunol. 2022; 77:102227. PMC: 9612402. DOI: 10.1016/j.coi.2022.102227. View

16.

Reyes R, Raghavan S, Hurlburt N, Introini V, Kana I, Jensen R . Broadly inhibitory antibodies against severe malaria virulence proteins. bioRxiv. 2024; . PMC: 10849712. DOI: 10.1101/2024.01.25.577124. View

17.

Leyendeckers H, Odendahl M, Lohndorf A, Irsch J, Spangfort M, Miltenyi S . Correlation analysis between frequencies of circulating antigen-specific IgG-bearing memory B cells and serum titers of antigen-specific IgG. Eur J Immunol. 1999; 29(4):1406-17. DOI: 10.1002/(SICI)1521-4141(199904)29:04<1406::AID-IMMU1406>3.0.CO;2-P. View

18.

Weiss G, Traore B, Kayentao K, Ongoiba A, Doumbo S, Doumtabe D . The Plasmodium falciparum-specific human memory B cell compartment expands gradually with repeated malaria infections. PLoS Pathog. 2010; 6(5):e1000912. PMC: 2873912. DOI: 10.1371/journal.ppat.1000912. View

19.

Rask T, Hansen D, Theander T, Pedersen A, Lavstsen T . Plasmodium falciparum erythrocyte membrane protein 1 diversity in seven genomes--divide and conquer. PLoS Comput Biol. 2010; 6(9). PMC: 2940729. DOI: 10.1371/journal.pcbi.1000933. View

20.

Weiss G, Crompton P, Li S, Walsh L, Moir S, Traore B . Atypical memory B cells are greatly expanded in individuals living in a malaria-endemic area. J Immunol. 2009; 183(3):2176-82. PMC: 2713793. DOI: 10.4049/jimmunol.0901297. View