Ab production against blood group A determinants was dependent on iNKT cells but independent of T cells. (A-B) Balb/c nude mice and B6 MHC C2D mice were immunized with human group A-RBCs 2 times per week. Balb/c and B6 WT mice were used as the respective controls. The serum anti-A Ab (IgM) concentrations at 2 weeks after the second immunization were measured by ELISA. Even after immunization, the serum anti-A Ab titers were not elevated in nude mice, but Ab concentrations significantly increased in C2D mice. Balb/c nude mice, n = 3; Balb/c WT mice, n = 3; B6 C2D mice, n = 4; B6 WT mice, n = 3. (C-D) Balb/c CD1d−/− mice and B6 Jα18−/− mice were immunized with human group A-RBCs 2 times per week. Balb/c and B6 WT mice served as the respective controls. The serum anti-A Ab levels were measured 2 weeks after the second immunization. The response of anti-A Abs was completely impaired in CD1d−/− mice and partially impaired in Jα18−/− mice. Average values ± SEM for the individual groups are shown. P values were shown to compare pre- and post-levels at the bottom of each figure. Balb/c CD1d−/− mice, n = 4; Balb/c WT mice, n = 3; B6 Jα18−/− mice, n = 5; B6 WT mice, n = 4. *P < .05 compared with the respective control mice.