Background Double negative B cells represent a heterogeneous compartment and expansion has been linked to systemic lupus erythematosus (SLE) in previous studies.1–3 Previously we found a novel CXCR5-CD19low subset in the DN compartment. Thus, we aimed to further characterize this population phenotypically and functionally.4
Methods For this study, we collected peripheral blood from a total of 79 patients with SLE and 80 healthy individuals as reference. We investigated baseline surface marker expression and Syk phosphorylation kinetics upon B cell receptor (BCR) stimulation of peripheral B cells and specifically the CXCR5-CD19low subset using flow cytometry. To check the subset for its capability of secreting antibodies, cell cultures were performed and soluble immunoglobulins were detected using a bead-based flow cytometry assay. Additionally, targeted RNAseq was performed.
Results We found that the subset of CXCR5-CD19low B cells can be found among DN and CD27+ memory B cells and was increased in SLE. Frequencies correlated with PBs frequencies. Surface marker expression of CD38, CD95 and CD71 and IgA and IgG suggest an activated and antigen experienced phenotype. BCR stimulation show a reduced responsiveness similar to the kinetic of PBs. The capacity to secret IgA ex vivo suggests that CXCR5-CD19low B cells are antibody secreting cells which was further supported by the finding of elevated transcriptional expression of PRDM1, XBP-1 and IRF4, transcription factors known to regulate plasmablasts (PB) differentiation.
Conclusions Summing up, besides bimodal expression of CD27 the subset of CXCR5- CD19low B cells shared various characteristics with PBs such as phenotype and functionality like antibody secretion and reduced BCR responsiveness. CXCR5- CD19low seemed to be related to plasmacytosis as suggested by the correlation with PB frequencies. Our data suggest that CXCR5-CD19low B cells are precursors of PBs and targeting this subset in SLE may have therapeutic value.
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Jenks SA, Cashman KS, Zumaquero E, Marigorta UM, Patel AV, Wang X, et al. Distinct Effector B Cells Induced by Unregulated Toll-like Receptor 7 Contribute to Pathogenic Responses in Systemic Lupus Erythematosus. Immunity 2018;49(4):725–39.e6.
Ruschil C, Gabernet G, Lepennetier G, Heumos S, Kaminski M, Hracsko Z, et al. Specific Induction of Double Negative B Cells During Protective and Pathogenic Immune Responses. Front Immunol 2020;11:606338.
Szelinski F, Stefanski AL, Schrezenmeier E, Rincon-Arevalo H, Wiedemann A, Reiter K, et al. Plasmablast-like Phenotype Among Antigen-Experienced CXCR5-CD19(low) B Cells in Systemic Lupus Erythematosus. Arthritis Rheumatol 2022;74(9):1556–68.
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