Antinuclear Abs are the hallmark of the autoimmune disease systemic lupus erythematosus (SLE). The ability of self reactive autoantibodies to bind to DNA and nucleosomes is partly conferred by an increased number of arginine and asparagine residues in the heavy chain third complementarity determining region. This increased content of cationic residues is primarily the result of unusual V H-DJ H rearrangements, which include DD fusions and D gene inversions. While self Ag-driven clonal expansion is a major contributor to the production of antinuclear Abs in lupus, we explore in this study the hypothesis that newly emerging B cells from autoimmune mice display more frequently these unusual V H-DJ H rearrangements. To this end, libraries of PCR-generated V H-DJ H junctions from MRL and C3H newborn livers were analyzed. When compared with the C3H controls, D and J H gene usage in MRL junctions suggests a greater frequency of secondary DJ H rearrangements in this strain. Furthermore, B cells from the autoimmune-prone MRL mice have significantly increased numbers of atypical V H-DJ H rearrangements (DD fusions and D inversions). Therefore, B cells from MRL mice manifest intrinsic defects that could confer an increased propensity to produce unusual V H-DJ H rearrangements early in ontogeny.