Background <p>Membranous nephropathy (MN) and idiopathic nephrotic syndrome (INS) are two B-cell mediated rare glomerular diseases that benefit from treatment with B-cell depleting anti-CD20 monoclonal antibody rituximab. Different B-cell dysregulations have been described in pediatric INS patients and in adults affected by MN. In adult MN patients, an increased level of mature-naïve cells and atypical memory B cells and a significant reduction in IgM memory and switched memory B cells have been previously described compared to healthy individuals. To date, there is no information available about B-cell immunophenotyping in pediatric MN.</p> Methods <p>In this monocentric retrospective case–control study, we analyzed by flow cytometry the B-cell profile in rituximab-naïve (<i>n</i> = 15) children affected by MN, compared with pediatric INS patients (<i>n</i> = 15) selected by propensity score matching, and both evaluated during active disease. Age-matched controls (<i>n</i> = 15) with non-immune-mediated kidney diseases were also characterized. Demographical, clinical, laboratory, and immunosuppressive treatment data were registered.</p> Results <p>We found that children with MN and INS had significantly higher circulating levels of total CD19⁺, mature-naïve, and atypical memory B cells and similar levels of transitional B cells when compared to age-matched controls. Circulating levels of total memory B cells, IgM memory B cells, and plasmablasts/plasmacells were significantly higher in INS patients compared to both MN patients and age-matched controls.</p> Conclusions <p>Our study indicated that children affected by MN had a specific B-cell profile and that high levels of memory B-cell subsets are specific to INS pediatric patients independently of proteinuria intensity.</p> Graphical abstract <p></p>