Transcriptomic Profile of TLR7-Induced B Cell Development in Lupus Mouse Spleen In Vivo, with and without IL-4 Interference

We investigated how IL-4 affects age-related B cell development in the context of TLR7 activation. Using single-cell RNA sequencing (scRNA-seq), we analyzed the transcriptomic profiles of autoimmune mice administered R848 with or without IL-4 treatment in vivo. Our results reveal that the differentiation of B cells into DN2 or DN4 stages is established early during the naive phase. IL-4 appears to redirect B cell development towards the transitional stage 2 (T2) and follicular (FO) pathways, while simultaneously inhibiting the formation of T3, marginal zone precursor, and marginal zone B cells in response to R848 stimulation. The transcriptomic data indicate that IL-4 promotes a T-dependent developmental program and suppresses a TLR/BCR-dependent program. IL-4 favors the differentiation of B cells into the precursor of DN4 lineage over the DN2 lineage. B cells were isolated from mice that have been treated in vivo with or without IL-4 (3 mice per group). All mice received in vivo R848 ip injection (2 days apart). scRNA-seq analysis was carried out using B cells from the spleen of these mice two days after the 2nd dose of injection.