CD19: a biomarker for B cell development, lymphoma diagnosis and therapy

Rituximab, the first monoclonal antibody against CD20 molecule, has revolutionized lymphoma therapy [1,2]. More monoclonal antibodies targeting different antigens are being developed for lymphoma therapy [3]. CD19 is specifically expressed in normal and neoplastic lymphoid cells. This review summarizes the molecular structure and functions of CD19 antigen as well as the clinical development of CD19 monoclonal antibodies for lymphoma therapy.The human CD19 antigen is a 95 kd transmembrane glycoprotein belonging to the immunoglobulin (Ig) superfamily [4,5]. It is encoded by the 7.41 kilobite cd19 gene located on the short arm of chromosome 16, 16p11.2 [6]. The gene contains 15 exons and codes for the CD19 molecule with 556 amino acids (Figure？1). There are more than one mRNA transcripts, though only two transcript isoforms have been isolated in vivo[5-7]. Structurally, the gene contains an unusually short 5'-untranslated region. The proximal cd19 promoter lacks a TATA box, and its major start sites are found within 50 bp of the initiation codon [8].CD19 is classified as a type I transmembrane protein, with a single transmembrane domain, a cytoplasmic C-terminus, and extracellular N-terminus. No significant homology exists between CD19 and other known proteins [9]. The extracellular element contains two C2-type Ig-like domains divided by a smaller potential disulfide linked non-Ig-like domain, as well as N-linked carbohydrate addition sites (Figure？2). The highly conserved cytoplasmic domain consists of 242 amino acids with nine tyrosine residues near the C-terminus [9-11]. Multiple studies have come to suggest that the biologic functions of CD19 are dependent on three cytoplasmic tyrosine residues – Y391, Y482 and Y513. Experiments have shown that substitution of phenylalanine for tyrosine at two of the positions, Y482 and Y513, leads to inhibited phosphorylation of the other seven tyrosines [12-14].CD19 was first identified as the B4 antigen of human B lymphocytes th