Signatures of B Cell Receptor Repertoire Following Pneumocystis Infection

Abstract

B cells play vital roles in host defense against Pneumocystis 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 Pneumocystis infection. We identified continuously increased plasma cells and an elevated ratio of (IgA + IgG) to (IgD + IgM) after infection. Moreover, Pneumocystis infection was associated with an increasing naïve B subset characterized by elevated expression of the transcription factor ATF3. 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 IGHV9-3 rose. Overall, these results present a detailed atlas of B cell transcriptional changes and BCR repertoire features in the context of Pneumocystis infection, which provides valuable information for finding diagnostic biomarkers and developing potential immunotherapeutic targets.

B-cell receptor repertoire sequencing: Deeper digging into the mechanisms and clinical aspects of immune-mediated diseases

“…A study shows that infection with Plasmodium alters the length of the CDR3 of the H chain and the preference of specific V genes, as well as the level of SHM in atypical memory B cells(atMBC) ( Braddom et al., 2021 ). Similar phenomenon of increased B cell cloning and reduced BCR diversity was also observed in patients with pneumocystis infection ( Sun et al., 2021 ).…”

Integrated multi-omics analyses reveal the altered transcriptomic characteristics of pulmonary macrophages in immunocompromised hosts with Pneumocystis pneumonia

“…Programmed death 1 (PD-1) deficiency can also promote the phagocytic capacity of macrophages and Th1/Th17 response, and improve Pneumocystis clearance (7). Furthermore, we have also elucidated the signatures of T cells and B cells repertoire profiling and their dynamics during Pneumocystis infection (8,9), confirming the contribution of adaptive immunity in controlling PCP.…”

“…murina were obtained from American Type Culture Collection (ATCC, Manassas, VA) and were maintained in CB-17 SCID mice as previously reported (6,7). To construct Pneumocystisinfected mouse models, each mouse was intratracheally instilled 1×10 6 cysts diluted in 100uL sterile PBS, while Pneumocystisuninfected control mice were administered 100 mL sterile PBS (8,64). Mice were humanely killed under anesthesia at indicated time points.…”

Characterization of B cell receptor H-CDR3 repertoire of spleen in PRV-infected mice

“…As the most variable region of the BCR repertoire, the CDR3 region determines the specificity of antigen binding to the BCR [14,25]. The CDR3 sequences exhibited large differences in the types and lengths in PRV infection groups in this study, which may be related to the immune response to specific antigens.…”

“…The aa sequences of CDR3s in the PRV infection groups were more convergent compared with that of control group, especially the CDR3s with 11 aa. The length of CDR3 was reported to be associated with antibody polyreactivity and autoimmunity, and naive B cells have longer CDR3 regions than mature cells [25,26].…”