The B lymphocyte compartment is comprised of B-1 and B-2 cells. The former is divided into B-1a, which express CD5, and B-1b cells which do not: both are self-renewing, although the mechanisms are yet to be identified. IL-10-/- mice were used to delineate the role of the B cell activator IL-10 in this process. Its absence had no effect on the total number of B-1 cells, but decreased that of B-1a cells (0.8 +/- 0.1 versus 1.7 +/- 0.2 x 10(6), p < 0.002), while increasing that of B-1b cells (1.9 +/- 0.4 versus 0.8 +/- 0.1 x 10(6), p < 0.03). The number of B-1a cells remained low in IL-10-injected IL-10-/- mice, whereas the excess of B-1b cells further increased (2.8 +/- 0.2 versus 1.6 +/- 0.4 x 10(6), p < 0.03). On the basis that Bax and Bad were augmented in B-1a cells, and Bcl-2 and Bcl-xL reduced, we conclude that the disappearance of B-1a cells, but not B-1b, in IL-10-/- mice results from their enhanced susceptibility to apoptosis. In addition, culture of IL-10-/- B-1a and B-1b cells in the presence of IL-10 drives more of the latter than of the former into cycle (p < 0.02). Therefore, IL-10 exerts two, complementary effects on the distribution of B-1 cell sub-populations, rescuing B-1a cells from apoptosis and encouraging B-1b cell proliferation.