BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is characterized by significant, but poorly understood immune and antibody responses. This study examines the spatial transcriptomes and microenvironmental niches of antibody-producing plasma cells and tertiary lymphoid structures (TLS) in IPF lungs, and the molecular pathways influencing antibody accumulation and pulmonary fibrosis. METHODS: Explant lung tissues from IPF patients and control normal lungs were used for spatial transcriptome assays and validating RNA-scope and immunofluorescence assays. Fibroblasts derived from IPF and control lungs were examined for their capability to attract plasma cells. Neutralizing antibodies were administered to investigate molecules affecting pulmonary plasma cell accumulation and fibrosis in bleomycin-treated mice. RESULTS: Human IPF lungs exhibited a remarkably widespread distribution of plasma cells and local antibodies in the fibrotic regions, disseminating from plasma cell-generating TLS. Novel mural cells wrapped the vessels in TLS regions, expressing CCR7 ligands that attracted T cells into TLS to promote plasma cell generation. Distinct IPF-associated fibroblasts further secreted CXCL12, providing an extramedullary niche to foster the dissemination and accumulation of plasma cells in the fibrotic regions. Neutralization of CCR7 ligands or CXCL12 reduced plasma cell and local antibody accumulation in the lungs of bleomycin-treated mice, leading to reduced TGFβ concentrations and alleviated pulmonary fibrosis. CONCLUSIONS: Plasma cells and local antibodies are widely distributed in the fibrotic regions of IPF lungs. Distinct subsets of IPF-associated mural cells and fibroblasts promote pathological plasma cell and antibody accumulation. These findings have potential implications for strategies aimed at targeting immune and antibody responses to combat IPF.