Anti-CD22/cal–mediated B-cell depletion in three immune settings of islet transplantation (allo, auto, and allo/auto). The percentage of B220+ cells was analyzed in the spleen of C57BL/6 and NOD mice at baseline and at 14 days after islet transplantation (n = 4 mice/condition). 1) In allo, BALB/c islets were transplanted into chemically induced C57BL/6 mice and treated with anti-CD22/cal, cal alone, or were left untreated (A1–5). Robust depletion of B220+ cells was evident 14 days after transplantation in mice treated with anti-CD22/cal compared with naïve untransplanted mice (baseline) (#P < 0.0001) and control antibody (cal)-treated mice (*P < 0.0001) (A1–5). 2) In auto, NOD.SCID islets were transplanted under the kidney capsule of spontaneously hyperglycemic NOD mice (B1–5). Complete B-cell depletion was observed 14 days after transplantation in mice treated with anti-CD22/cal compared with naive untransplanted (#P < 0.0001) and control-treated mice (*P < 0.0001) (B1–5), whereas no depleting effect was found when mice were treated with cal or were untreated (NS). 3) In allo/auto, BALB/c islets were transplanted into spontaneously hyperglycemic NOD mice (C1–5). A complete B-cell depletion occurred 14 days after transplantation in mice treated with anti-CD22/cal compared with untransplanted (#P < 0.0001), cal-treated (*P < 0.0001), and untreated mice (*P < 0.0001) (C1–5), whereas no differences in B-cell peripheral percentage were observed in mice treated with cal or untreated (NS) (C4–5).