Lymphotoxin beta receptor mice display altered B- and T-cell subpopulations in the bone marrow and peritoneal cavity after 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 infection. Here, we investigated the bone marrow (BM) and peritoneal cavity (PerC) compartments of LTβR mice during infection, demonstrating perturbed B-cell and T-cell subpopulations in the absence of LTβR signaling. 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.