Last Updated: 24/11/2025
Regulation and function of B cells during malaria infection- Resubmission
Objectives
The long-term goal of this study is to determine how protective antibody responses are generated and maintained in mice after Plasmodium infection, and to utilize this information to understand why antibody-mediated immunity is slow to develop in humans.
The specific objectives are to:
- characterize heterogeneous populations of memory B cells after P. yoelii 17X infection in mice and determine their origin;
- determine the function of distinct subsets of memory B cells after secondary infection; and
- determine whether the two identified populations of memory T cells expressing follicular helper–associated markers can differentiate into functional T follicular helper cells capable of supporting antibody production during secondary infection, and to evaluate whether these populations are required for protective immunity following pathogen challenge.
University of Arkansas for Medical Sciences (UAMS), United States
The protozoan parasite Plasmodium is the causative agent of malaria, which remains one of the most prominent public health challenges in the world today. Plasmodium-specific antibody responses are important for protecting against subsequent reinfections in humans and mice. However, while mice are protected after a single infection, protective immunity is slow to develop in humans due to the requirement of repeated infections for the generation of protective antibodies. Plasmodium-specific memory B cells are generated after infection in mice and humans; however, surprisingly little information is available regarding their specificity, phenotype, origin and affinity for malarial antigens. The preliminary studies indicate that there are layers of heterogeneity within the memory B cell pool after Plasmodium infection and the researchers hypothesize that this heterogeneity in the memory B cell pool contributes to functional diversity in a secondary infection. To accomplish these goals the researchers have developed innovative tools to track parasite- specific B cell responses at the cellular level utilizing parasites engineered to express hen egg-white lysozyme (HEL). Using HEL-specific transgenic B cells and a novel magnetic-bead based enrichment technique the team can monitor and track the fate of antigen-specific B cells after infection with HEL expressing parasites. These innovative tools and approaches will provide valuable insight into understanding how protective immunity against Plasmodium is generated, is maintained, and functions in a secondary immune response and will identify key components involved in this process.
- Article - Bhlhe40 limits early IL-10 production from CD4+ T cells during Plasmodium yoelii 17X infection
- Article - ICOS Expression Is Required for Maintenance but Not the Formation of Germinal Centers in the Spleen in Response to Plasmodium yoelii Infection
- Article - IgM+ and IgM– memory B cells represent heterogeneous populations capable of producing class-switched antibodies and germinal center B cells upon rechallenge with P. yoelii
- Article - The spleen: “epicenter” in malaria infection and immunity
Dec 2015 — Nov 2021
$2.43M
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