Immunogenetics

, Volume 35, Issue 2, pp 102–111 | Cite as

Structure of the genes encoding the CD19 antigen of human and mouse B lymphocytes

  • Liang-Ji Zhou
  • David C. Ord
  • Sidne A. Omori
  • Thomas F. Tedder
Original Articles

Abstract

CD19 is a B lymphocyte cell-surface marker that is expressed early during pre-B-cell differentiation with expression persisting until terminal differentiation into palsma cells. CD19 is a member of Ig gnee superfamily with two extreacellular Ig-like domains separated amino acid cytoplasmic domain. In this study, Southern blot analysis revelaed that the human and mouse CD19 genes were compact single copy genes. Both the human and mouse CD19 genes were isolated and the nucleotide sequences flanking each exon were determined. Both genes were composed of 15 exons and spanned ∼8 kilobases (kb) of DNA in human and ∼6 kb in mouse. The positions of exon-intron boundaries were identical between human and mouse and correlated with the putative functional domains of the CD19 protein. The 200 bp region 5′ of the putative translation initiation AUG codon as well conserved in sequence between human and mouse and contained potential trasncription regulatory elements. In addition, the 3′ untranslated regions (UT) of the CD19 genes following the termination codon were conservedf in sequence. The high level conservation of nucleotide sequences between species in all exons and 5′ and 3′ UT suggests that expression of the CD19 gene may be regulated in a similar fashion in human and mouse.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Aebi, M. and Weissmann, C.: Precision and orderlliess in splicing. Trends Genet 3: 102, 1987Google Scholar
  2. Anderson, K. C., Slaughenhoupt, B., Bates, M. P., Pinkus, G., Schlossman, S. F., and Nadler, L. M.: Expression of human B cell-associated antigens on leukemias and lymphomas: A model of human B cell differentiation. Blood 63: 1424–1433, 1984Google Scholar
  3. Anderson, S. J., Chou, H. D., and Loh, D. Y.: A conserved sequence in the T-cell receptor β-chain promoter region. Proc Natl Acad Sci USA 85: 3551–3554, 1988Google Scholar
  4. Benton, W. D. and Davis, R. W.: Screening lambda gt recombinant clones by hybridization to single plaques in situ. Science 196: 180–182, 1977Google Scholar
  5. Bradbury, L., Kansas, G., Levy, S., Evans, R. L., and Tedder, T. F.: CD19 is a component of a signal transducing complex on the surface of B cells that included CD21, TAPA-1 and Leu-13. FASEB J 5: A611, 1991Google Scholar
  6. Diamond, D. J., Clayton, L. K., Sayre, P. H., and Reinherz, E. L.: Exon-intron organization and sequence comparison of human and murine T11 (CD2) genes. Proc Natl Acad Sci USA 85: 1615–1619, 1988Google Scholar
  7. Fuse, A., Fujita, T., Yasumitsu, H., Kashima, N., Hasegawa, K., and Taniguchi, T.: Organization and structure of the mouse interleukin-2 gene. Nucleic Acids Res 12: 9323–9331, 1984Google Scholar
  8. Garvin, A. M., Pawar, S., Marth, J. D., and Perlmutter, R. M.: Structure of the murine Ick gene and its rearrangement in a murine lymphoma cell line. Mol Cell Biol 8: 3058–3064, 1988Google Scholar
  9. Hermanson, G. G., Briskin, M., Sigman, D., and Wall, R.: Immunoglobulin enhancer and promoter motifs 5′t′ of the B29 B-cell-specific gene. Proc Natl Acad Sci USA 86: 7341–7345, 1989Google Scholar
  10. Kashiwamura, S., Koyama, T., Matsuo, T., Steinmetz, M., Kimoto, M., and Sakaguchi, N.: Structure of the murine mb-1 gene encoding a putative sIgM-associated molecule. J Immunol 145: 337–343, 1990Google Scholar
  11. Klemsz, M. J., McKercher, S. R., Celada, A., Van Beveren, C., and Maki, R. A.: The macrophage and B-cell specific transcription factor PU.1 is related to the ets oncogene. Cell 61: 113–124, 1990Google Scholar
  12. Kudo, A. and Melchers, F.: A second gene, VpreB in the λ5 locus of the mouse, which appears to be selectively expressed in pre-B lymphocytes. EMBO J 6: 2267–2272, 1987Google Scholar
  13. Kudo, A., Sakaguchi, N.m and Melchers, F.: Organization of the murine Ig-related λ5 gene transcribed selectively in pre-B lymphocytes. EMBO J 6: 103–107, 1987Google Scholar
  14. Lenardo, M. J. and Baltimore, D.: nf-κB: A pleiotropic mediator of inducible and tissue-specific gene control. Cell 58: 227–229, 1989Google Scholar
  15. Libermann, T. A., Lenardo, M. J., and Baltimore, D.: Involvement of a second lymphoid-specific enhancer element in the regulation of immunoglobulin heavy-chain gene expression. Mol Cell Biol 10: 3155–3162, 1990Google Scholar
  16. Maniatis, T., Fritsch, E., and Sambrook, J.: Molecular Cloning: A Laboratory Manual, Cold Spring Harbor Laboratory, Cold Spring Harbor, 1–545, 1982Google Scholar
  17. Matsumoto, A. K., Kopicky-Burd, J., Carter, R. H., Tuveson, D. A., Tedder, T. F., and Fearon, D. T.: Intersection of the complement and immune systems: A signal transduction complex of the B lymphocyte containing complement receptor type 2 and CD19. J Exp Med 173: 55–64, 1991Google Scholar
  18. Melton, D., Krieg, P., Rebagliati, M., Maniatis, T., Zinn, K., and Green, M.: Efficient in vitro synthesis of biologically active RNA and RNA hybridization probes from plasmids containing a bacteriophage SP6 promoter. Nucleic Acids Res 12: 7035–7056, 1984Google Scholar
  19. Nadler, L., Anderson, K., Marti, G., Bates, M., Park, E., Daley, J., and Schlossman, S.: B4, a human B lymphocyte-associated antigen expressed on normal, mitogen activated, and malignant B lymphocytes. J Immunol 131: 244–250, 1983Google Scholar
  20. Nadler, L., Korsmeyer, S., Anderson, K., Boyd, A., Slaughenhoupt, B., Park, E., Jensen, J., Coral, F., Mayer, R., Sallan, S., Ritz, J., and Schlossman, S.: B cell origin of non-T cell acute lymphoblastic leukemia. A model for discrete stages of neoplastic and normal pre-B cell differentiation. J Clin Invest 74: 332–340, 1984Google Scholar
  21. Nelsen, B., Kadesch, T., and Sen, R.: Complex regulation of the immunoglobulin μ heavy-chain gene enhancer: μB, a new determinant of enhancer function. Mol Cell Biol 10: 3145–3154, 1990Google Scholar
  22. Pesando, J. M., Bouchard, L. S., and McMaster, B. E.: CD19 is functionally and physically associated with surface immunoglobulin. J Exp Med 170: 2159–2164, 1989Google Scholar
  23. Pezzuto, A., Dorken, B., Rabinovitch, P., Ledbetter, J., Moldenhauer, G., and Clark, E.: CD19 monoclonal antibody HD37 inhibits anti-immunoglobulin-induced B cell activation and proliferation. J Immunol 138: 2793–2799, 1987Google Scholar
  24. Rigby, P., Dieckmann, M., Rhodes, C., and Berg, P.: Labeling DNA to high specific activity in vitro by nick translation. J Mol Biol 113: 237–251, 1977Google Scholar
  25. Sanger, F., Nicklen, S., and Coulson, A.: DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci USA 74: 5463–5467, 1977Google Scholar
  26. Scriever, F., Freedman, A. S., Freeman, G., Messner, E., Lee, G., Daley, J., and Nadler, L. M.: Isolated human follicular dendritic cells display a unique antigenic phenotype. J Exp Med 169: 2043–2058, 1989Google Scholar
  27. Sleasman, J. W., Tedder, T. F., and Barrett, D. J.: Combined immunodeficiency due to the selective absence of CD4 inducer T lymphocytes. Clin Immunol Immunopathol 55: 401–417, 1990Google Scholar
  28. Smale, S. T. and Baltimore, D.: The “initiator” as a transcription control element. Cell 57: 103–113, 1989Google Scholar
  29. Southern, E.: Detection of specific sequence among DNA fragments separated by gel electrophoresis. J Mol Biol 98: 503–527, 1975Google Scholar
  30. Stamenkovic, I. and Seed, B.: CD19, the earliest differentiation antigen of the B cell lineage, bears three extracellular immunoglobulin-like domains and an Epstein-Barr Virus-related cytoplasmic tail. J Exp Med 168: 1205–1210, 1988Google Scholar
  31. Stashenko, P., Nadler, L. M., Hardy, R., and Schlossman, S. F.: Expression of cell surface markers after human B lymphocyte activation. Proc Natl Acad Sci USA 78: 3848–3852, 1981Google Scholar
  32. Tedder, T. and Isaacs, C.: Isolation of cDNAs encoding the CD19 antigen of human and mouse B lymphocytes:: A new member of the immunoglobulin superfamily. J Immunol 143: 712–717, 1989Google Scholar
  33. Tedder, T., Klejman, G., Schlossman, S., and Saito, H.: Structure of the gene encoding the human B lymphocyte differentiation antigen CD20 (B1). J Immunol 142: 2560–2568, 1989Google Scholar
  34. Van den Elsen, P., Georgopoulos, K., Shepley, B. A., Orkin, S., and Terhorst, C.: Exon/intron organization of the genes coding for the delta chains of the human and murine T-cell receptor/T3 complex. Proc Natl Acad Sci USA 83: 2944–2948, 1986Google Scholar
  35. Wahl, G., Stern, M., and Stark, G.: Efficient transfer of large DNA fragment from agarose gels. Proc Natl Acad Sci USA 76: 3683–3687, 1979Google Scholar
  36. Williams, A. F. and Barclay, A. N.: The immunoglobulin superfamily-domains for cell surface recognition. Annu Rev Immunol 88: 381–405, 1988Google Scholar
  37. Zhou, L.-J. Ord, D. C., and Tedder, T. F.: Structure and domain organization of the CD19 antigen of human, mouse and guinea pig B lymphocytes: Conservation of the extensive cytoplasmic domain. J Immunol 147: 1424–1432, 1991Google Scholar

Copyright information

© Springer-Verlag 1992

Authors and Affiliations

  • Liang-Ji Zhou
    • 1
  • David C. Ord
    • 1
  • Sidne A. Omori
    • 2
  • Thomas F. Tedder
    • 1
  1. 1.Division of Tumor Immunology, Danna-Farber Cancer Institute and Department of PathologyHarvard Medical SchoolBostonUSA
  2. 2.Depart of Microbiology and Immnunology, Scool of MedicineUniversity of California Los AngelesLos AngelesUSA

Personalised recommendations