Abstract Systemic lupus erythematosus is characterized by the spontaneous production of IgG autoantibodies in patients and lupus-prone mice. In this study, we investigated the effect of the Sle1 lupus susceptibility locus on the peripheral development of 56R+ anti-DNA transgenic B cells by tracking 56R+B cells in mice without (B6.56R) or with the Sle1 locus (B6.Sle1.56R). Compared to B6.56R mice, B6.Sle1.56R mice exhibited increased class-switched IgG2a anti-DNA antibodies in their serum, encoded by the transgene. Interestingly, within the spleen, Sle1 facilitated the development of these cells into clusters of IgG2a class-switched B cells juxtaposed to CD4+ T cells within extrafollicular sites. Through sequence analysis of B cell hybridomas, we also found that B cells from B6.Sle1.56R mice are inefficient at immunoglobulin heavy chain and light chain editing. Thus, the immunoglobulin heavy chains in Sle1.56R+ B cells are partnered more often with cationic light chains that facilitate DNA binding. Taken together, these findings indicate that the Sle1 lupus susceptibility locus may facilitate the emergence of anti-DNA B cells by subduing B cell receptor revision, and possibly by shaping extrafollicular development of effector B cells, though the precise molecular mechanisms await further study.