The prevalence of systemic lupus erythematosus (SLE) is far higher in females than in males and numerous investigations to understand this gender bias have been performed, which propose as casual actors genetic predispositions and sex hormones effects. We will describe in this review how the sex hormones estrogen and prolactin influence B cell maturation and selection, permitting B cells to mature to immunocompetence in a mouse model of lupus. Finally, we will discuss the relevance and implications of these results for human disease.