CD19 Gene

The CD19 gene (CD19 stands for "Cluster of Differentiation 19) is a protein-coding gene located on chromosome 16p11.2. Alternative splicing results in multiple transcript variants encoding different isoforms.

The CD19 gene encodes a member of the immunoglobulin gene superfamily (see also CD19). Expression of the CD19 cell surface protein is restricted to B-cell lymphocytes. The protein is areliable marker for pre-B cells. The protein is required for normal differentiation of B-1 cells. CD19 is required for normal B cell differentiation and proliferation in response to antigen challenge (Carter RH et al 1992) and further it is necessary for the setting of normal concentrations of serum immunoglobulins as well as for the production of high affinity antibodies in response to antigens. Its expression decreases during terminal B-cell differentiation in antibody-secreting plasma cells.

The protein has two N-terminal extracellular Ig-like domains separated by a non-Ig-like domain, a hydrophobic transmembrane domain, and a large C-terminal cytoplasmic domain. CD19 functions as a co-receptor for the B-cell antigen receptor (BCR) complex on B lymphocytes (de Rie MA et al.). The CD19 protein forms a complex with several membrane proteins (CD19 complex), including CD21 a complement receptor type 2 as well as CD81 (tetraspanin). This complex lowers the threshold for B cell activation triggered by an antigen. Activation of this B cell antigen receptor complex activates the phosphatidylinositol 3-kinase signaling pathway and subsequent release of intracellular calcium ions ((Buhl AM et al.1997).

Activated signaling pathways include the BCR signaling pathway.

The CD19 protein is a target of chimeric antigen receptor (CAR) T cells (see also Kochenderfer JN et al. 2013; Imura Y et al. 2020).

With blinatumomab, a bispecific T cell-enhancing molecule(BiTE antibody) that specifically binds to CD19 expressed on the surface of B-lineage-derived cells and to CD3 expressed on the surface of T cells is on the market. It activates endogenous T cells by linking CD3 in the T-cell receptor (TCR) complex with CD19 on benign and malignant B cells.

Mutations in this gene are associated with the disease CVID3 (Common Variable Immunodeficiency 3).

1. Buhl AM et al. Qualitative regulation of B cell antigen receptor signaling by CD19: selective requirement for PI3-kinase activation, inositol-1,4,5-trisphosphate production and Ca2+ mobilization. J Exp Med 186:1897-910.
2. Carter RH et al (1992) CD19: lowering the threshold for antigen receptor stimulation of B lymphocytes. Science 256(5053):105-107.
3. de Rie MA et al (1989) Regulatory role of CD19 molecules in B-cell activation and differentiation. Cell Immunol 118:368-381.
4. Imura Y et al (2020) CD19-targeted CAR regulatory T cells suppress B cell pathology without GvHD. JCI Insight 5:e136185.
5. Kochenderfer JN et al (2013) Treating B-cell cancer with T cells expressing anti-CD19 chimeric antigen receptors. Nat Rev Clin Oncol 10:267-276.