Using, among others, splenocyte single-cell transcriptome analysis, and 2 lupus models crossed with the KO for Bank1, a transgenic model of Tlr7 (TLR7.tg6) (28), and a TLR7-pathway imiquimod-induced (IMQ-induced) disease model (29), we show that Bank1 has a fundamental role in the differentiation of key B cell populations in autoimmunity and B cell functions dependent on TLR7 signaling. Here, TLR7 is linked to systemic lupus erythematosus.