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Gene Review

CD19  -  CD19 molecule

Homo sapiens

Synonyms: B-lymphocyte antigen CD19, B-lymphocyte surface antigen B4, B4, CVID3, Differentiation antigen CD19, ...
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Disease relevance of CD19

  • There has been interest in generating T cells expressing chimeric artificial receptors (CARs) targeting CD19/CD20 antigens to treat B-cell lymphomas [1].
  • Monoclonal chronic lymphocytic leukemia (CLL)-phenotype cells are detectable in 3.5% of otherwise healthy persons using flow cytometric analysis of CD5/CD20/CD79b expression on CD19-gated B cells [2].
  • All cases were confirmed as B-lineage lymphoblastic leukemia by virtue of expression of CD19 and/or CD22, lack of T-cell antigens, and lack of surface-membrane immunoglobulin (Ig) [3].
  • A novel bispecific single-chain fusion protein, DT2219, was assembled consisting of the catalytic and translocation domains of diphtheria toxin (DT(390)) fused to two repeating sFv subunits recognizing CD19 and CD22 and expressed in Escherichia coli [4].
  • The blasts of acute myeloid leukemia (AML) with t(8;21)(q22;q22) frequently express the B-cell antigen CD19, which is regulated by B cell-specific activator protein (BSAP) encoded by the PAX5 gene, a protein important for B-cell lineage commitment and development [5].

Psychiatry related information on CD19


High impact information on CD19

  • Regulation of B lymphocyte responses to foreign and self-antigens by the CD19/CD21 complex [9].
  • Studies of signal transduction have begun to determine the basis for the coreceptor activities of CD19 [9].
  • CD21 binds the C3d fragment of activated C3 that becomes covalently attached to targets of complement activation, and CD19 co-stimulates signaling through the antigen receptor, membrane immunoglobulin [9].
  • The CD19/CR2/TAPA-1 complex of B lymphocytes: linking natural to acquired immunity [10].
  • CD19, a B cell-restricted membrane protein of the immunoglobulin superfamily that associates with the antigen receptor complex, may help the B cell meet this requirement [10].

Chemical compound and disease context of CD19


Biological context of CD19


Anatomical context of CD19

  • Here we demonstrate complete correlation between the expression pattern of the CD19 gene and the B-cell-specific transcription factor BSAP in a large panel of B-lymphoid cell lines [19].
  • The CD19 protein is expressed on the surface of all B-lymphoid cells with the exception of terminally differentiated plasma cells and has been implicated as a signal-transducing receptor in the control of proliferation and differentiation [19].
  • In contrast to BCL-1 cells, normal BALB/c splenocytes or mouse splenocyte/myeloma hybridoma cell lines did not (1) express any transcripts that hybridized to the human CD19 cDNA probe, (2) react with B43/anti-CD19 MoAb, or (3) express the 69-Kd protein that reacts with the anti-human CD19 MoAb J3-119 [20].
  • Moreover, this site is occupied by BSAP in vivo in a CD19-expressing B-cell line but not in plasma or HeLa cells [19].
  • In this study, two of the CD19-associated proteins were identified as TAPA-1, which is expressed on most cell types, and Leu-13, which is expressed on subsets of lymphoid cells [21].

Associations of CD19 with chemical compounds

  • The complex, which was immunoprecipitated also with anti-CD19, could be dissociated by Nonidet P-40, accounting for its absence in previous studies of CR2 [16].
  • 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 [17].
  • Despite identical molecular mass of 95 kDa, this tyrosine phosphorylated p95 molecule was not CD19, the proto-oncogene Vav, or the adaptator Gab1 [22].
  • Alterations in B cell development are most likely due to engagement of pre-B cell receptor-mediated or other regulatory pathways by hCR2 in a CD19- and possibly C3 ligand-dependent manner [23].
  • In the current studies, we incubated purified small resting B cells with 100-nm latex beads bearing various combinations of CD21 ligands and mAbs to CD19, CD35, and the Ag receptor [24].

Physical interactions of CD19

  • The unsuitability of CD38 to perform as a receptor is obviated through close interaction with the B-cell-receptor (BCR) complex and CD19 [25].
  • Here, we examine whether coligation of the B cell Ag receptor (BCR) with the complement (C3)-binding CD21/CD19/CD81 costimulatory complex can enhance the escape of human B cells from Fas-induced death [26].
  • Gel shift assays demonstrated SP1 and Egr-1 binding to the CD19 GC box, while unknown nuclear proteins bound the PyG and AT boxes [27].
  • CD19 is a 95-kD B-cell surface marker that contains a consensus binding motif for PI3Kp85 in the cytoplasmic domain and recruits PI3K activity in activated B cells [28].
  • Engaging CD19 or target of an antiproliferative antibody 1 on human B lymphocytes induces binding of B cells to the interfollicular stroma of human tonsils via integrin alpha 4/beta 1 and fibronectin [29].

Enzymatic interactions of CD19

  • Co-crosslinking of CD19 and BCR was shown to enhance B-cell activation due to the recruitment of further signaling molecules to the activator complex by the phosphorylated tyrosine residues of CD19 [30].

Regulatory relationships of CD19

  • Engagement of the CD19 receptor on human B-lineage leukemia cells activates LCK tyrosine kinase and facilitates radiation-induced apoptosis [31].
  • This CPM induction was specifically enhanced by CD19 or CD40 ligation [32].
  • CD19/Lyn complex formation also regulates phosphorylation of CD22 and FcgammaRIIB, which inhibit B cell signal transduction through the recruitment of the SHPI and SHIP phosphatases [33].
  • In experiments using PMA as a T cell independent mitogen, it was found that ligation of CD19 inhibited proliferation of B cells costimulated with low doses of PMA plus G28.5 (CD40) antibody, but enhanced the response to higher (mitogenic) doses with or without costimulation with G28 [34].
  • In B cells, the increase in [Ca2+]i and resulting proliferation induced by crosslinking either the CD19 or Bgp95 receptors was inhibited by coupling these molecules to CD45 [35].

Other interactions of CD19

  • In contrast, CD22 internalization and degradation was unaffected by stimulation of B cell lines with phorbol dibutyrate or ligation of other components of the B cell receptor complex (e.g. CD19, sIgM) with mAbs [36].
  • Role of complement-binding CD21/CD19/CD81 in enhancing human B cell protection from Fas-mediated apoptosis [26].
  • By using affinity purified CDw40 protein we have also demonstrated that it is antigenically distinct from other B cell-associated Ag, including the six differentiation clusters CD19 to CD24 [37].
  • Participation of other molecules, not examined in this study (CD19 and CD37), in these supramolecular structures cannot be ruled out [38].
  • METHODS: The percentage expression and mean fluorescence intensity of CR2 (and three additional markers: CD19, CD69, and a standard antigen designation: HLA-DR) was measured on CD20+ B-cells using a two-color flow cytometric assay [39].

Analytical, diagnostic and therapeutic context of CD19

  • Western blot analysis of BCL-1 whole cell lysates with the anti-human CD19 MoAb J3-119 showed a single 69-Kd protein band, which was not detected by the negative control MoAb G19.4 (anti-CD3) [20].
  • Immunoprecipitation studies with B cell lines solubilized by digitonin have shown CD19 to be part of a multimolecular complex that includes CD21 (CR2) and other unidentified proteins [21].
  • A bispecific recombinant immunotoxin, DT2219, targeting human CD19 and CD22 receptors in a mouse xenograft model of B-cell leukemia/lymphoma [4].
  • We investigated, by quantitative flow cytometry, the expression of CD79b, CD5 and CD19 in cells from a variety of B-cell disorders to see whether this analysis adds further information useful to the diagnosis and characterization of these diseases [40].
  • The study was carried out by triple immunostaining with directly conjugated monoclonal antibodies (MoAb) against CD79b, CD5 and CD19 and quantitative estimation of the antigens per cell assessed with standard microbeads (Quantum Simply Cellular) [40].


  1. T lymphocytes redirected against the {kappa} light chain of human immunoglobulin efficiently kill mature B lymphocyte-derived malignant cells. Vera, J., Savoldo, B., Vigouroux, S., Biagi, E., Pule, M., Rossig, C., Wu, J., Heslop, H.E., Rooney, C.M., Brenner, M.K., Dotti, G. Blood (2006) [Pubmed]
  2. Inherited predisposition to CLL is detectable as subclinical monoclonal B-lymphocyte expansion. Rawstron, A.C., Yuille, M.R., Fuller, J., Cullen, M., Kennedy, B., Richards, S.J., Jack, A.S., Matutes, E., Catovsky, D., Hillmen, P., Houlston, R.S. Blood (2002) [Pubmed]
  3. Prognostic significance of CD34 expression in childhood B-precursor acute lymphocytic leukemia: a Pediatric Oncology Group study. Borowitz, M.J., Shuster, J.J., Civin, C.I., Carroll, A.J., Look, A.T., Behm, F.G., Land, V.J., Pullen, D.J., Crist, W.M. J. Clin. Oncol. (1990) [Pubmed]
  4. A bispecific recombinant immunotoxin, DT2219, targeting human CD19 and CD22 receptors in a mouse xenograft model of B-cell leukemia/lymphoma. Vallera, D.A., Todhunter, D.A., Kuroki, D.W., Shu, Y., Sicheneder, A., Chen, H. Clin. Cancer Res. (2005) [Pubmed]
  5. Expression of B cell-specific activator protein/PAX5 in acute myeloid leukemia with t(8;21)(q22;q22). Valbuena, J.R., Medeiros, L.J., Rassidakis, G.Z., Hao, S., Wu, C.D., Chen, L., Lin, P. Am. J. Clin. Pathol. (2006) [Pubmed]
  6. Therapeutic efficacy of FcgammaRI/CD64-directed bispecific antibodies in B-cell lymphoma. Honeychurch, J., Tutt, A.L., Valerius, T., Heijnen, I.A., Van De Winkel, J.G., Glennie, M.J. Blood (2000) [Pubmed]
  7. D8/17 and CD19 expression on lymphocytes of patients with acute rheumatic fever and Tourette's disorder. Weisz, J.L., McMahon, W.M., Moore, J.C., Augustine, N.H., Bohnsack, J.F., Bale, J.F., Johnson, M.B., Morgan, J.F., Jensen, J., Tani, L.Y., Veasy, L.G., Hill, H.R. Clin. Diagn. Lab. Immunol. (2004) [Pubmed]
  8. Neuropeptide Y plasma levels and immunological changes during academic stress. Guidi, L., Tricerri, A., Vangeli, M., Frasca, D., Riccardo Errani, A., Di Giovanni, A., Antico, L., Menini, E., Sciamanna, V., Magnavita, N., Doria, G., Bartoloni, C. Neuropsychobiology (1999) [Pubmed]
  9. Regulation of B lymphocyte responses to foreign and self-antigens by the CD19/CD21 complex. Fearon, D.T., Carroll, M.C. Annu. Rev. Immunol. (2000) [Pubmed]
  10. The CD19/CR2/TAPA-1 complex of B lymphocytes: linking natural to acquired immunity. Fearon, D.T., Carter, R.H. Annu. Rev. Immunol. (1995) [Pubmed]
  11. CD19-targeting liposomes containing imatinib efficiently kill Philadelphia chromosome-positive acute lymphoblastic leukemia cells. Harata, M., Soda, Y., Tani, K., Ooi, J., Takizawa, T., Chen, M., Bai, Y., Izawa, K., Kobayashi, S., Tomonari, A., Nagamura, F., Takahashi, S., Uchimaru, K., Iseki, T., Tsuji, T., Takahashi, T.A., Sugita, K., Nakazawa, S., Tojo, A., Maruyama, K., Asano, S. Blood (2004) [Pubmed]
  12. Clinical pharmacokinetics of the CD19 receptor-directed tyrosine kinase inhibitor B43-Genistein in patients with B-lineage lymphoid malignancies. Chen, C.L., Levine, A., Rao, A., O'Neill, K., Messinger, Y., Myers, D.E., Goldman, F., Hurvitz, C., Casper, J.T., Uckun, F.M. Journal of clinical pharmacology. (1999) [Pubmed]
  13. 99mTc-CD19 monoclonal antibody is not useful for imaging of B cell non-Hodgkin's lymphoma. Vervoordeldonk, S.F., Heikens, J., Goedemans, W.T., Merle, P.A., von dem Borne, A.E., van Royen, E.A., Slaper-Cortenbach, I.C., van Oers, R.H. Cancer Immunol. Immunother. (1996) [Pubmed]
  14. Globotriaosyl ceramide modulates interferon-alpha-induced growth inhibition and CD19 expression in Burkitt's lymphoma cells. Maloney, M.D., Binnington-Boyd, B., Lingwood, C.A. Glycoconj. J. (1999) [Pubmed]
  15. Large scale manufacturing of B43(anti-CD19)-genistein for clinical trials in leukemia and lymphoma. Myers, D.E., Sicheneder, A., Clementson, D., Dvorak, N., Venkatachalam, T., Sev, A.R., Chandan-Langlie, M., Uckun, F.M. Leuk. Lymphoma (1998) [Pubmed]
  16. Intersection of the complement and immune systems: a signal transduction complex of the B lymphocyte-containing complement receptor type 2 and CD19. Matsumoto, A.K., Kopicky-Burd, J., Carter, R.H., Tuveson, D.A., Tedder, T.F., Fearon, D.T. J. Exp. Med. (1991) [Pubmed]
  17. 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. Buhl, A.M., Pleiman, C.M., Rickert, R.C., Cambier, J.C. J. Exp. Med. (1997) [Pubmed]
  18. Engraftment of human hematopoietic precursor cells with secondary transfer potential in SCID-hu mice. Chen, B.P., Galy, A., Kyoizumi, S., Namikawa, R., Scarborough, J., Webb, S., Ford, B., Cen, D.Z., Chen, S.C. Blood (1994) [Pubmed]
  19. The promoter of the CD19 gene is a target for the B-cell-specific transcription factor BSAP. Kozmik, Z., Wang, S., Dörfler, P., Adams, B., Busslinger, M. Mol. Cell. Biol. (1992) [Pubmed]
  20. In vivo efficacy of B43 (anti-CD19)-pokeweed antiviral protein immunotoxin against BCL-1 murine B-cell leukemia. Uckun, F.M., Chelstrom, L.M., Irvin, J.D., Finnegan, D., Gunther, R., Young, J., Kuebelbeck, V., Myers, D.E., Houston, L.L. Blood (1992) [Pubmed]
  21. The CD19/CD21 signal transducing complex of human B lymphocytes includes the target of antiproliferative antibody-1 and Leu-13 molecules. Bradbury, L.E., Kansas, G.S., Levy, S., Evans, R.L., Tedder, T.F. J. Immunol. (1992) [Pubmed]
  22. Activation of the EBV/C3d receptor (CR2, CD21) on human B lymphocyte surface triggers tyrosine phosphorylation of the 95-kDa nucleolin and its interaction with phosphatidylinositol 3 kinase. Barel, M., Le Romancer, M., Frade, R. J. Immunol. (2001) [Pubmed]
  23. Expression of human complement receptor type 2 (CD21) in mice during early B cell development results in a reduction in mature B cells and hypogammaglobulinemia. Marchbank, K.J., Kulik, L., Gipson, M.G., Morgan, B.P., Holers, V.M. J. Immunol. (2002) [Pubmed]
  24. Modulation of signaling via the B cell antigen receptor by CD21, the receptor for C3dg and EBV. Luxembourg, A.T., Cooper, N.R. J. Immunol. (1994) [Pubmed]
  25. CD38 is a signaling molecule in B-cell chronic lymphocytic leukemia cells. Deaglio, S., Capobianco, A., Bergui, L., Dürig, J., Morabito, F., Dührsen, U., Malavasi, F. Blood (2003) [Pubmed]
  26. Role of complement-binding CD21/CD19/CD81 in enhancing human B cell protection from Fas-mediated apoptosis. Mongini, P.K., Jackson, A.E., Tolani, S., Fattah, R.J., Inman, J.K. J. Immunol. (2003) [Pubmed]
  27. In vivo footprinting and mutational analysis of the proximal CD19 promoter reveal important roles for an SP1/Egr-1 binding site and a novel site termed the PyG box. Riva, A., Wilson, G.L., Kehrl, J.H. J. Immunol. (1997) [Pubmed]
  28. The protein product of the proto-oncogene c-cbl forms a complex with phosphatidylinositol 3-kinase p85 and CD19 in anti-IgM-stimulated human B-lymphoma cells. Beckwith, M., Jorgensen, G., Longo, D.L. Blood (1996) [Pubmed]
  29. Engaging CD19 or target of an antiproliferative antibody 1 on human B lymphocytes induces binding of B cells to the interfollicular stroma of human tonsils via integrin alpha 4/beta 1 and fibronectin. Behr, S., Schriever, F. J. Exp. Med. (1995) [Pubmed]
  30. Integration of activatory and inhibitory signals in human B-cells. Sármay, G., Koncz, G., Gergely, J. Immunol. Lett. (1996) [Pubmed]
  31. Engagement of the CD19 receptor on human B-lineage leukemia cells activates LCK tyrosine kinase and facilitates radiation-induced apoptosis. Waddick, K.G., Chae, H.P., Tuel-Ahlgren, L., Jarvis, L.J., Dibirdik, I., Myers, D.E., Uckun, F.M. Radiat. Res. (1993) [Pubmed]
  32. CD40 and B cell antigen receptor dual triggering of resting B lymphocytes turns on a partial germinal center phenotype. Galibert, L., Burdin, N., de Saint-Vis, B., Garrone, P., Van Kooten, C., Banchereau, J., Rousset, F. J. Exp. Med. (1996) [Pubmed]
  33. CD19 regulates intrinsic B lymphocyte signal transduction and activation through a novel mechanism of processive amplification. Fujimoto, M., Poe, J.C., Hasegawa, M., Tedder, T.F. Immunol. Res. (2000) [Pubmed]
  34. CD19 regulation of human B cell responses. B cell proliferation and antibody secretion are inhibited or enhanced by ligation of the CD19 surface glycoprotein depending on the stimulating signal used. Callard, R.E., Rigley, K.P., Smith, S.H., Thurstan, S., Shields, J.G. J. Immunol. (1992) [Pubmed]
  35. CD45 regulates signal transduction and lymphocyte activation by specific association with receptor molecules on T or B cells. Ledbetter, J.A., Tonks, N.K., Fischer, E.H., Clark, E.A. Proc. Natl. Acad. Sci. U.S.A. (1988) [Pubmed]
  36. Constitutive endocytosis and degradation of CD22 by human B cells. Shan, D., Press, O.W. J. Immunol. (1995) [Pubmed]
  37. The human B lymphocyte and carcinoma antigen, CDw40, is a phosphoprotein involved in growth signal transduction. Paulie, S., Rosén, A., Ehlin-Henriksson, B., Braesch-Andersen, S., Jakobson, E., Koho, H., Perlmann, P. J. Immunol. (1989) [Pubmed]
  38. Supramolecular complexes of MHC class I, MHC class II, CD20, and tetraspan molecules (CD53, CD81, and CD82) at the surface of a B cell line JY. Szöllósi, J., Horejsí, V., Bene, L., Angelisová, P., Damjanovich, S. J. Immunol. (1996) [Pubmed]
  39. In vivo decrease in the expression of complement receptor 2 on B-cells in HIV infection. Scott, M.E., Landay, A.L., Lint, T.F., Spear, G.T. AIDS (1993) [Pubmed]
  40. Quantitative analysis of CD79b, CD5 and CD19 in mature B-cell lymphoproliferative disorders. Cabezudo, E., Carrara, P., Morilla, R., Matutes, E. Haematologica (1999) [Pubmed]
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