The invention concerns treatment methods using anti-CD22 monoclonal antibodies with unique physiologic properties. In particular, the invention concerns methods for the treatment of B-cell malignancies and autoimmune diseases by administering an effective amount of a blocking anti-CD22 monoclonal antibody specifically binding to the first two Ig-like domains, or to an epitope within the first two Ig-like domains of native human CD22 (hCD22).