The invention relates to novel combination therapies involving BLyS or BLyS/APRIL inhibition and anti-CD20 agents for the treatment of autoimmune diseases. One preferred method is where the BLyS antagonist is a Fc-fusion protein which can be a TACI-Fc-fusion protein comprising the extracellular domain of TACI or a functional fragment thereof, a BAFF—R-Fc-fusion protein comprising the extracellular domain of BAFF—R or a functional fragment thereof, or a BCMA-Fc-fusion protein comprising the extracellular domain of BCMA or a functional fragment thereof. In the methods of the present invention some of anti-CD20 agents contemplated include RITUXAN®, (rituximab),ocrelizumab, ofatumumab (HuMax-CD20®), TRU-015, and DXL625, although any agent that binds to CD 20 may be suitable. The methods of the present invention reduce the levels of B cells in patients in need of such reduction, such as those suffering from autoimmune diseases.