# Lymphotoxin beta receptor-/- mice display altered B- and T-cell subpopulations in the bone marrow and peritoneal cavity after Toxoplasma gondii infection

## TL;DR

Mice lacking the Lymphotoxin beta receptor show immune system changes in bone marrow and peritoneal cavity after Toxoplasma gondii infection.

## Contribution

Identifies novel roles for LTβR signaling in B- and T-cell homeostasis and pathogen defense.

## Key findings

- LTβR-/- mice show altered B-cell and T-cell subpopulations in bone marrow and peritoneal cavity.
- LTβR deficiency leads to a skewed plasma cell compartment and altered T-cell subset frequencies.
- LTβR-/- mice exhibit upregulated TNFα-NF-κB signaling potentially compensating for LTβR absence.

## Abstract

Lymphotoxin β receptor (LTβR/TNFRSF3) signaling plays a crucial role in immune defense. Notably, LTβR-deficient (LTβR-/-) mice exhibit severe defects in innate and adaptive immunity against various pathogens and succumb to Toxoplasma gondii infection. Here, we investigated the bone marrow (BM) and peritoneal cavity (PerC) compartments of LTβR-/- mice during T. gondii infection, demonstrating perturbed B-cell and T-cell subpopulations in the absence of LTβR signaling. T. gondii infection disrupted BM lymphopoiesis, depleting early and mature B cells in WT mice, whereas mature B cells remained present in LTβR-/- BM. LTβR-/- BM also exhibited reduced MHCII+ monocytes and a plasma cell compartment skewed toward IgM+ rather than IgA+ cells. In addition, BM Tcell subsets were altered, exhibiting decreased double-negative (CD4-/CD8-) and increased CD4+ and CD8+ T-cell frequencies. Analysis of the BM transcriptome revealed diminished interferon responses but an upregulated TNFα-NF-κB signaling signature in uninfected and infected LTβR-/- mice, potentially compensating for the absence of LTβR signaling. LTβR-/- mice displayed an altered B-1a to B-1b ratio and a predominant presence of neutrophils in the PerC. In summary, we identified novel immunological alterations in the BM and PerC compartments of LTβR-/- mice, which suggest new roles for LTβR signaling in B- and T-cell homeostasis, migration, and pathogen defense.