CD19, a 95-kDa member of the immunoglobulin super-family, is exclusively expressed on B lymphocytes and serves as a critical co-receptor for B cell antigen receptor (BCR) signal transduction. Co-ligation of CD19 with the BCR can synergistically enhance calcium release, mitogen-activated protein kinase activity, and cell proliferation. However, in certain situations, CD19-deficient animals display hyper-responsiveness, indicating potential negative regulatory functions in BCR signaling. Its abnormal expression can lead to B cell-related diseases [5].

CD19 is a B-lineage-specific transmembrane glycoprotein, expressed on over 95% B-cell malignancies, making it an ideal target for immune therapies. Adoptive T-cell therapy with anti-CD19 chimeric antigen receptor (CAR)-expressing T cells can effectively treat advanced B-cell malignancies, eradicating lymphoma and normal B cells in murine models [4]. CD19-targeted CAR-T cell therapies have shown major responses in patients with relapsed B-cell malignancies, though often accompanied by a systemic inflammatory reaction syndrome [3]. New anti-CD19 CAR T cell therapies, like CD19-BBz(86), aim to reduce severe cytokine-release syndrome (CRS) and neurotoxicity while maintaining potent antilymphoma activity [1]. Additionally, CD19 is emerging as a promising target in autoimmune diseases such as systemic sclerosis, with CD19-targeted therapies like CAR T cells and Uplizna® showing potential [2].

In summary, CD19 plays a crucial role in BCR signaling, with both positive and negative regulatory functions. Its expression pattern and function make it an attractive target for treating B-cell malignancies and certain autoimmune diseases. Studies, including those using in vivo models like murine models, have revealed its significance in these disease areas, highlighting its potential as a therapeutic target for improving patient outcomes.

References:

1. Ying, Zhitao, Huang, Xue F, Xiang, Xiaoyu, Zhu, Jun, Chen, Si-Yi. 2019. A safe and potent anti-CD19 CAR T cell therapy. In Nature medicine, 25, 947-953. doi:10.1038/s41591-019-0421-7. https://pubmed.ncbi.nlm.nih.gov/31011207/

2. Komura, Kazuhiro. 2024. CD19: a promising target for systemic sclerosis. In Frontiers in immunology, 15, 1454913. doi:10.3389/fimmu.2024.1454913. https://pubmed.ncbi.nlm.nih.gov/39421745/

3. Ramos, Carlos A, Savoldo, Barbara, Dotti, Gianpietro. . CD19-CAR trials. In Cancer journal (Sudbury, Mass.), 20, 112-8. doi:10.1097/PPO.0000000000000031. https://pubmed.ncbi.nlm.nih.gov/24667955/

4. Kochenderfer, James N, Yu, Zhiya, Frasheri, Dorina, Restifo, Nicholas P, Rosenberg, Steven A. 2010. Adoptive transfer of syngeneic T cells transduced with a chimeric antigen receptor that recognizes murine CD19 can eradicate lymphoma and normal B cells. In Blood, 116, 3875-86. doi:10.1182/blood-2010-01-265041. https://pubmed.ncbi.nlm.nih.gov/20631379/

5. Li, Xinchen, Ding, Ying, Zi, Mengting, Chen, Shun, Xu, Yuekang. 2017. CD19, from bench to bedside. In Immunology letters, 183, 86-95. doi:10.1016/j.imlet.2017.01.010. https://pubmed.ncbi.nlm.nih.gov/28153605/