Signatures of B Cell Receptor Repertoire Following Pneumocystis Infection

Abstract

B cells play vital roles in host defense against <i>Pneumocystis</i> infection. However, the features of the B cell receptor (BCR) repertoire in disease progression remain unclear. Here, we integrated single-cell RNA sequencing and single-cell BCR sequencing of immune cells from mouse lungs in an uninfected state and 1-4 weeks post-infection in order to illustrate the dynamic nature of B cell responses during <i>Pneumocystis</i> infection. We identified continuously increased plasma cells and an elevated ratio of (IgA + IgG) to (IgD + IgM) after infection. Moreover, <i>Pneumocystis</i> infection was associated with an increasing naïve B subset characterized by elevated expression of the transcription factor <i>ATF3</i>. The proportion of clonal expanded cells progressively increased, while BCR diversity decreased. Plasma cells exhibited higher levels of somatic hypermutation than naïve B cells. Biased usage of V(D)J genes was observed, and the usage frequency of <i>IGHV9-3</i> rose. Overall, these results present a detailed atlas of B cell transcriptional changes and BCR repertoire features in the context of <i>Pneumocystis</i> infection, which provides valuable information for finding diagnostic biomarkers and developing potential immunotherapeutic targets.