CD4 T Cell-Derived IL-21 Is Critical for Sustaining Plasmodium Infection-Induced Germinal Center Responses and Promoting the Selection of Memory B Cells with Recall Potential

Jordan T Johnson; Fionna A Surette; Graham R Ausdal; Manan Shah; Allen M Minns; Scott E Lindner; Ryan A Zander; Noah S Butler

doi:10.4049/jimmunol.2300683

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CD4 T Cell-Derived IL-21 Is Critical for Sustaining Plasmodium Infection-Induced Germinal Center Responses and Promoting the Selection of Memory B Cells with Recall Potential

Journal article

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CD4 T Cell-Derived IL-21 Is Critical for Sustaining Plasmodium Infection-Induced Germinal Center Responses and Promoting the Selection of Memory B Cells with Recall Potential

Jordan T Johnson, Fionna A Surette, Graham R Ausdal, Manan Shah, Allen M Minns, Scott E Lindner, Ryan A Zander and Noah S Butler

The Journal of immunology (1950), Vol.212(9), pp.1467-1478

05/01/2024

DOI: 10.4049/jimmunol.2300683

PMCID: PMC11018477

PMID: 38477614

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https://scholarsphere.psu.edu/resources/e6a1deb5-fcfe-4e7d-97b0-5e14482126a8/downloads/37507View

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Abstract

Development of Plasmodium-specific humoral immunity is critically dependent on CD4 Th cell responses and germinal center (GC) reactions during blood-stage Plasmodium infection. IL-21, a cytokine primarily produced by CD4 T cells, is an essential regulator of affinity maturation, isotype class-switching, B cell differentiation, and maintenance of GC reactions in response to many infection and immunization models. In models of experimental malaria, mice deficient in IL-21 or its receptor IL-21R fail to develop memory B cell populations and are not protected against secondary infection. However, whether sustained IL-21 signaling in ongoing GCs is required for maintaining GC magnitude, organization, and output is unclear. In this study, we report that CD4+ Th cells maintain IL-21 expression after resolution of primary Plasmodium yoelii infection. We generated an inducible knockout mouse model that enabled cell type-specific and timed deletion of IL-21 in peripheral, mature CD4 T cells. We found that persistence of IL-21 signaling in active GCs had no impact on the magnitude of GC reactions or their capacity to produce memory B cell populations. However, the memory B cells generated in the absence of IL-21 exhibited reduced recall function upon challenge. Our data support that IL-21 prevents premature cellular dissolution within the GC and promotes stringency of selective pressures during B cell fate determination required to produce high-quality Plasmodium-specific memory B cells. These data are additionally consistent with a temporal requirement for IL-21 in fine-tuning humoral immune memory responses during experimental malaria.

Details

Title: Subtitle: CD4 T Cell-Derived IL-21 Is Critical for Sustaining Plasmodium Infection-Induced Germinal Center Responses and Promoting the Selection of Memory B Cells with Recall Potential
Creators: Jordan T Johnson - University of Iowa
Fionna A Surette - University of Iowa
Graham R Ausdal - University of Iowa
Manan Shah - University of Iowa
Allen M Minns - Pennsylvania State University
Scott E Lindner - Pennsylvania State University
Ryan A Zander - University of Iowa
Noah S Butler - University of Iowa
Resource Type: Journal article
Publication Details: The Journal of immunology (1950), Vol.212(9), pp.1467-1478
DOI: 10.4049/jimmunol.2300683
PMID: 38477614
PMCID: PMC11018477
NLM abbreviation: J Immunol
eISSN: 1550-6606
Grant note: R01 GM125907 / NIGMS NIH HHS
Language: English
Electronic publication date: 03/13/2024
Date published: 05/01/2024
Academic Unit: Molecular Physiology and Biophysics; Microbiology and Immunology
Record Identifier: 9984572379602771

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