In this study, normal adult mice carried B220(high) conventional B cells in the spleen and liver, but carried both B220(high) and B220(low) in the bone marrow. However, at the neonatal stage, only B220(low) unconventional B cells were found in all these organs. This pattern continued up to 2 weeks after birth, and at this stage autoantibodies were detected in the sera. This phenomenon was seen in all tested young mice (1-2 weeks), irrespective of their gender. Furthermore, at older stages (more than 20 weeks), B220(low) cells reappeared in the spleen and liver, and these B220(low) cells became dominant in the bone marrow. Autoantibodies also reappeared in the sera of these older mice. Cell-sorting experiments revealed that B220(low) cells were able to produce autoantibodies upon lipopolysaccharide stimuli in vitro. These results suggest that B220(low) cells appear at both neonatal and older stages as physiological responses and eventually produce autoantibodies.