CD19 is a 95 kDa type-I transmembrane glycoprotein and a member of the immunoglobulin superfamily. It is extensively expressed on B cells during most stages of B-cell differentiation, with expression levels decreasing as B cells terminally differentiate into plasma cells. Genetic mapping places CD19 at the 16p11.2 locus on chromosome 16, where it encodes a 540 amino acid protein. This protein features two extracellular C-type IgSF domains and a large cytoplasmic tail of approximately 240 residues, which shows significant conservation between mice and humans.
CD19 functions as a signal-amplifying coreceptor, with its expression limited to B cells and follicular dendritic cells. It is part of a multimolecular complex on the B cell surface that includes CD21 (complement receptor type 2, CR2), the tetraspanin CD81, and CD225. Through its interaction with CD21, CD19 acts as a signal transducing component for antigens bound by complement. The co-ligation of the B cell receptor (BCR) and the CD19/CD21 complex significantly lowers the activation threshold of B cells by approximately two orders of magnitude.
Recognizing its role in B cell biology, CD19 has emerged as a potential target for monoclonal antibody therapy. Early data have shown its potential in B-cell depletion, presenting an attractive treatment option for autoimmune diseases and malignant B-cell lymphomas. The rationale for CD19 as a target for immunotherapy includes: (1) its expression on the majority of B-cell malignancies; (2) its early expression in the B-cell lineage, preceding even CD20; (3) its efficient internalization in lymphoma tumor models; and (4) its potential involvement in the development of B-cell cancers.