Genetic mapping reveals Nfkbid as a central regulator of humoral immunity to Toxoplasma gondii

• DOI: 10.1371/journal.ppat.1010081
• Publication Date: 2021-12-06T18:28:03Z
• Authors: Scott P. Souza; Samantha D. Splitt; Juan C. Sànchez-A...; Julia A. Alvarez; Jessica N. Wilson; Safuwra Wizzard; Zheng Luo; Nicole Baumgarth; Kirk D. C. Jensen
• Keywords: Humoral immunity; Isotype

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