Genetic Mapping Reveals Nfkbid As a Central Regulator of Humoral Immunity to Toxoplasma Gondii

Overview

Journal PLoS Pathog

Specialty Microbiology

Date 2021 Dec 6

PMID 34871323

Citations 6

Authors

Scott P Souza

Samantha D Splitt

Juan C Sanchez-Arcila

Julia A Alvarez

Jessica N Wilson

Safuwra Wizzard

Zheng Luo

Nicole Baumgarth

Kirk D C Jensen

Affiliations

Soon will be listed here.

Abstract

Protective immunity to parasitic infections has been difficult to elicit by vaccines. Among parasites that evade vaccine-induced immunity is Toxoplasma gondii, which causes lethal secondary infections in chronically infected mice. Here we report that unlike susceptible C57BL/6J mice, A/J mice were highly resistant to secondary infection. To identify correlates of immunity, we utilized forward genetics to identify Nfkbid, a nuclear regulator of NF-κB that is required for B cell activation and B-1 cell development. Nfkbid-null mice ("bumble") did not generate parasite-specific IgM and lacked robust parasite-specific IgG, which correlated with defects in B-2 cell maturation and class-switch recombination. Though high-affinity antibodies were B-2 derived, transfer of B-1 cells partially rescued the immunity defects observed in bumble mice and were required for 100% vaccine efficacy in bone marrow chimeric mice. Immunity in resistant mice correlated with robust isotype class-switching in both B cell lineages, which can be fine-tuned by Nfkbid gene expression. We propose a model whereby humoral immunity to T. gondii is regulated by Nfkbid and requires B-1 and B-2 cells for full protection.

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