CD22 (also known as Siglec-2) belongs to the Siglec family of glycan-recognition proteins and negatively regulates B-cell receptor-mediated signaling. CD22 protein is known to be down-regulated in the B cells of patients with chronic lymphocytic leukemia (CLL). However, the mechanism regulating the transcription of CD22 is incompletely understood. In this study, we defined the minimal promoter region of the human CD22 gene, and systematically identified the proteins binding to the minimal promoter by DNA affinity-purification from the nuclear extracts of B cell lines and LC-MS/MS.