CD19, from bench to bedside

- CD19 is a double-edged sword, which functions as both positive and negative regulator in BCR signaling.
- The biochemical basis of CD19 as BCR regulator is the recruitment of secondary signaling molecules like PI3K via its cytoplasmic tail, which may be inside or outside of lipid rafts, depending on extracellular environments, to either promote or suppress BCR signals from antigens respectively.
- Abnormal CD19 expression on B cells is associated with tumor development and autoimmune diseases. Thus CD19 can be as a valid therapeutic target for these diseases.

As a 95-kDa member of the immunoglobulin super-family expressed exclusively on B lymphocytes, CD19 is a critical co-receptor for B cell antigen receptor (BCR) signal transduction. Co-ligation of CD19 with the BCR synergistically enhances calcium release, mitogen-activated protein kinase activity and cell proliferation. However, CD19 deficient animals also display hyper-responsiveness under certain circumstances, indicating potential negative regulatory functions in BCR signaling. Thus CD19, like many other signaling molecules, is a double-edged sword and its abnormal expression can result in B cell related diseases. Here in this review, we summarize the latest development on the major functions of CD19 as both positive and negative regulator of BCR signaling in different situations and highlight the correlation and mechanisms of disturbed CD19 expression with autoimmune diseases and B cell lymphomas. Hopefully, the knowledge derived could shed an interesting light on the mechanistic insights of this important B cell surface molecule in both physiological and pathological conditions.