Disclosed are compositions and methods comprising combinations of anti-CD74 and anti-CD20 antibodies or antigen-binding fragments thereof. The antibody combination may also be used with a therapeutic agent that is attached to antibody or fragment thereof or separately administered. The therapeutic agent may be an immunomodulator, a cytokine, a toxin or other known therapeutic agent. Preferably, the anti-CD74 and anti-CD20 antibody or fragment are part of a DNL complex. More preferably, combination therapy with the anti-CD74 and anti-CD20 antibody or fragment is more effective than either antibody alone, or the combination of unconjugated antibodies. Administration of combination induces apoptosis of target cells in diseases in which CD74 is overexpressed, such as solid tumors, B-cell lymphomas or leukemias, autoimmune disease, immune dysfunction disease or diabetes. Preferably, the target cells are B cells.