Description
CD19 (Cluster of Differentiation 19), also known as B-lymphocyte surface antigen B4, is a type 1 transmembrane glycoprotein belonging to immunoglobulin (Ig) subfamily that serves as a biomarker for normal and neoplastic B cells (1,2). CD19 is a co-receptor for the B cell receptor (BCR) signaling complex and has a critical role in regulating B cell signaling and immune response (1,2). The CD19 protein contains an extracellular N-terminus containing two C2 Ig-like domains separated by a helical non-Ig domain, a single pass transmembrane domain, and a highly conserved cytoplasmic C-terminal domain (1,2). The human CD19 protein, encoded by the CD19 gene located on chromosome 16p11.2, is 556 amino acids (aa) in length with a calculated theoretical molecular weight (MW) of 61 kDa and an observed molecular weight of 95 kDa (1-3). CD19 associates with other molecules - CD21, CD81, and CD225 - to form the BCR co-complex, also called the CD19 complex, through CD21 binding to the complement C3d complex (1-3). Complement C3d bridges the BCR with the CD19 complex into lipid rafts of the plasma membrane (1-3). CD19 is capable of modulating B cell development through both BCR-dependent and -independent signaling (1-3). Upon BCR activation, the tyrosine residues of CD19's cytoplasmic tail recruits multiple kinases including Lyn, Vav, and PI3K, amplifying BCR-mediated immune signaling and B cell activation (1-3).
Considering the role of CD19 in BCR signaling and its expression in development from pre-B cells through plasma cells, it is understandable that CD19 dysfunction and abnormal expression is associated with numerous B cell malignancies and autoimmune disorders (1-5). CD19 expression is typically observed at relatively normal levels in B cell acute lymphoblastic leukemia (B-ALL) and chronic lymphoblastic leukemia (CLL) but is often reduced other types of lymphoma including diffuse large B cell lymphoma (DLBCL) and follicular lymphoma (FL) (1,2). On the other hand, CD19 expression is typically increased in autoimmune disorders such as systemic sclerosis (SSc) and multiple sclerosis (MS) as modeled by experimental autoimmune encephalomyelitis (EAE) (2). CD19 has become a therapeutic molecular target for the treatment of B cell lymphomas and autoimmune disorders using monoclonal antibodies (mAbs), bi-specific T cell engaging (BiTE) antibodies, and CD19-specific chimeric antigen receptor (CAR) T cells (1,2,4-6). Although anti-CD19 CAR T cell therapy has become the standard for the treatment of B cell malignancies, patients may experience relapse due to resistance mechanisms (6). Strategies to improve efficacy and limit relapse include combination of CAR T cell therapy with immune checkpoint inhibitors like anti-PD-1 (4,6).
References
1. Wang K, Wei G, Liu D. CD19: a biomarker for B cell development, lymphoma diagnosis and therapy. Exp Hematol Oncol. 2012;1(1):36. https://doi.org/10.1186/2162-3619-1-36
2. Li X, Ding Y, Zi M, et al. CD19, from bench to bedside. Immunol Lett. 2017;183:86-95. https://doi.org/10.1016/j.imlet.2017.01.010
3. Wentink MWJ, van Zelm MC, van Dongen JJM, Warnatz K, van der Burg M. Deficiencies in the CD19 complex. Clin Immunol. 2018;195:82-87. https://doi.org/10.1016/j.clim.2018.07.017
4. Frigault MJ, Maus MV. State of the art in CAR T cell therapy for CD19+ B cell malignancies. J Clin Invest. 2020;130(4):1586-1594. https://doi.org/10.1172/JCI129208
5. Penack O, Koenecke C. Complications after CD19+ CAR T-Cell Therapy. Cancers (Basel). 2020;12(11):3445. https://doi.org/10.3390/cancers12113445
6. Bouziana S, Bouzianas D. Anti-CD19 CAR-T cells: Digging in the dark side of the golden therapy. Crit Rev Oncol Hematol. 2021;157:103096. https://doi.org/10.1016/j.critrevonc.2020.103096
Bioinformatics
Entrez |
Mouse Human |
Uniprot |
Human Human Human Human |
Product By Gene ID |
930 |
Alternate Names |
- B4
- B-lymphocyte antigen CD19
- B-lymphocyte surface antigen B4
- CD19 antigen
- CD19 molecule
- CVID3
- Differentiation antigen CD19
- MGC12802
- T-cell surface antigen Leu-12
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