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

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 <i>Toxoplasma gondii</i> infection. Here, we investigated the bone marrow (BM) and peritoneal cavity (PerC) compartments of LTβR^-/- mice during <i>T. gondii</i> infection, demonstrating perturbed B-cell and T-cell subpopulations in the absence of LTβR signaling. <i>T. gondii</i> 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.