| First Author | Souza SP | Year | 2021 |
| Journal | PLoS Pathog | Volume | 17 |
| Issue | 12 | Pages | e1010081 |
| PubMed ID | 34871323 | Mgi Jnum | J:316317 |
| Mgi Id | MGI:6835678 | Doi | 10.1371/journal.ppat.1010081 |
| Citation | Souza SP, et al. (2021) Genetic mapping reveals Nfkbid as a central regulator of humoral immunity to Toxoplasma gondii. PLoS Pathog 17(12):e1010081 |
| abstractText | 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-kappaB 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. |
