CD19 is the hallmark differentiation antigen of the B lineage. Its early expression has implicated a role for CD19 during the antigen-independent phases of B-cell development, whereas in mature B cells CD19 can act synergistically with surface immunoglobulin to induce activation(1). We have generated CD19-deficient mice and found that development of conventional B cells is unperturbed. However, mature CD19(-/-) B cells show a profound deficiency in responding to protein antigens that require T-cell help. This is accompanied by a lack of germinal centre formation and affinity maturation of serum antibodies. Thus CD19 is crucial for both initial B-cell activation by T-cell-dependent antigens and the maturation and/or selection of the activated cells into the memory compartment. An impairment in ligand-driven selection may also be responsible for the observation of a striking reduction in the B-1 (formerly Ly-1) B-cell subset, thought to develop under the control of self-antigens and bacterial antigens (reviewed in ref. 2).