Portraying B cells in IPF: a focus on micro-environment and IgA secretion

<bold>Rationale:</bold> The role of B cells and IgA in IPF remains to be fully determined. Recent studies suggest an elevation of IgA in IPF patients, with higher levels associated with increased mortality. IPF lung is characterized by the presence of IgA⁺ B cells and an increase in IgA⁺ memory B cells. However, B cell location, especially antibodies-secreting cells (ASC), remains elusive, alongside IgA⁺ B cells and the relative contribution of the different isotypes. <bold>Methods:</bold> We stained lung slides for CD79a, CD138, IgA and Blimp1, CD19, IgA, proSP‑C and Krt5 and analysed them with Visiopharm, QuPath and CytoMAP. Primary B cells from IPF explant were analysed in flow cytometry to decipher their phenotype as well as IgA1, IgA2 and IgG isotypes. <bold>Results:</bold> Total B cells and ASC were increased in IPF as compared to controls. Isotype determination by flow cytometry showed that IgA1+ cells were predominant in IPF. We observed that IgA⁺ B cells were close to Krt5⁺ honeycomb cysts and hyperplastic AECII (Figure 1), further confirmed by proximity studies. Discussion: Our findings elucidate the distribution of B cells and ASC in the IPF lung. We observed that lymphoid aggregates were mostly IgA⁻ and that IgA⁺ cells and ASC had a subepithelial location. Proximity analysis demonstrated that these cells were close to remodelled epithelium. These results highlight that there is an activation of B cells and an IgA production in remodelled areas of the IPF lung. <fig><object-id>erj;64/suppl_68/PA4416/F1</object-id><object-id>F1</object-id><object-id>F1</object-id><graphic></graphic></fig>