Lyn Tyrosine Kinase Signals Cell Cycle Arrest in Mouse and Human B-Cell Lymphoma

  • R. H. Scheuermann
  • E. Racila
  • J. W. Uhr
Part of the Current Topics in Microbiology and Immunology book series (CT MICROBIOLOGY, volume 194)


Tumor dormancy is an operational term used to describe a prolonged quiescent state in which tumor cells are present, but tumor progression is not clinically apparent. In order to study the mechanisms underlying tumor dormancy, we have utilized two murine models of dormancy with an aggressive murine B-cell lymphoma (BCL1) [1–3]. In the first model, BALB/c mice are immunized to the idiotype (Id) of the BCL1 immunoglobulin (Ig) before challenge with BCL1. In the second model, antibody to various epitopes on the BCL1 Ig (an IgM-λ) are injected into SCID mice before or after challenge with BCL1. In naive BALB/c or SCID mice, the tumor grows primarily in the spleen and splenomegaly is detected approximately one month after challenge with 3 x 104106 BCL1 cells. In Idimmune mice injected with 106 BCL1, 70% do not develop splenomegaly by day 60. We have used this time period as an arbitrary cut-off and have considered such mice to harbor dormant tumor. When the spleens of Id-immunized BALB/c mice that display tumor dormancy are examined, a population of dormant lymphoma cells (DLC) can be isolated by multiparameter cell sorting. The rarity of λ light chain in BALB/c mice (usually less than 0.5%) has facilitated isolation of the DLC. Examination of these cells shows that they are physiologically different from those of BCL1 cells growing in non-immune BALB/c.


Cell Cycle Arrest SCID Mouse Induce Cell Cycle Arrest Daudi Cell Tumor Dormancy 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Krolick, K.A., Uhr, J.W., Slavin, S. & Vitetta, E.S. In vivo therapy of a murine B cell tumor (BCL1) using antibodv-ricin A chain immunotoxins. (1982) J. Exp. Med. 155, 1797–1809.PubMedCrossRefGoogle Scholar
  2. 2.
    George, J.J.T., Tutt, A.L. & Stevenson, F.K., Anti-idiotvpic mechanisms involved in suppression of a mouse B cell lymphoma BCL1.. (1987) J Immunol. 138, 628–634.Google Scholar
  3. 3.
    Yefenof, E., Picker, L.J., Scheuermann, R.H., Tucker, T.F., Vitetta, E.S. & Uhr, J.W. Cancer dormancy: isolation and characterization of dormant lymphoma cells. (1993) ProcNatlAcad.Sci.USA. 90, 1829–1833.Google Scholar
  4. 4.
    Scheuermann, R.H., Racila, E. Tucker, T., Yefenof, E., Street, N.E., Vitetta, E.S., Picker, L.J. & Uhr, J.W. Lyn tyrosine kinase signals cell cycle arrest but not apoptosis in B-lineage lymphoma cells (1994) Proc Natl Acad.Sci. U.SA. 91, 4048–4052.CrossRefGoogle Scholar
  5. 5.
    Cambier, J.C. & Campbell, K.S. Membrane immunoglobulin and its accomplices: new lessons from an old receptor. (1992) FASEB J. 6, 3207–3217.Google Scholar
  6. 6.
    Kim, K.-M., Alber, G., Weiser, P. & Reth, M. Signaling function of the B-cell antigen receptors. (1993) Immunol Rev. 132, 125–145.PubMedCrossRefGoogle Scholar
  7. 8.
    Ghetie, M.-A., Picker, L.J., Richardson, J.A., Tucker, K., Uhr, J.W. & Vitetta, E.S. Anti-CD 19 inhibits the growth of human B-cell tumor lines in vitro and of Daudi cells in SCID mice bv inducing cell cvcle arrest. (1994) Blood 83, 1–9Google Scholar
  8. 9.
    van Noesel, C.J.M., Lankester, A.C., van Schijndel, G.M.W. & Van Lier, R.A.W. The CR2/CD19 complex on human B cells contains the src-family kinase Lyn. (1993) InterntlImmunol. 5, 699–705.CrossRefGoogle Scholar
  9. 10.
    Brown, S.L., Miller, R.A. & Levy, R. Anti-idiotype antibody therapy of B-cell lymphoma (1989) Seminars in Oncology 16, 199–210.PubMedGoogle Scholar
  10. 11.
    Vitetta, E. S., Thorpe, P.E. & Uhr, J. W. Immunotoxins: magic bullets or misguided missiles? (1993) Immunol.Today 14, 252–259.PubMedCrossRefGoogle Scholar
  11. 12.
    Boulet, I., Ralph, S., Stanley, E., Lock, P., Dunn, A.R., Green, S.P. & Phillips, W.A. Lipopolvsaccharide- and interferon-gamma-induced expression of hck and lvn tyrosine kinases in murine bone marrow-derived macrophages (1992) Oncogene 7, 703–710.PubMedGoogle Scholar
  12. 13.
    Cichowski, K., McCormick, F. & Brugge, J.S. p21rasGAP association with Fvn. Lvn. and Yes in thrombin-activated platelets (1992) J.Biol.Chem. 267, 5025–5028.PubMedGoogle Scholar
  13. 14.
    O’Connor, R., Torigoe, T., Reed, J.C. & Santoli, C. Phenotvpic changes induced by interleukin-2 (IL-2) and IL-3 in an immature T-lymphocvtic leukemia are associated with regulated expression of IL-2 receptor beta chain and of protein tyrosine kinases LCK and LYN (1992) Blood 80, 1017–1025PubMedGoogle Scholar
  14. 15.
    Bielke, W., Ziemieki, A., Kappos, L. & Miescher, G.C. Expression of the B cell-associated tyrosine kinase gene Lvn in primary neuroblastoma tumours and its modulation during the differentiation of neuroblastoma cell lines (1992) Biochem.Biophys.Res.Comm. 186, 1403–1409.PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1995

Authors and Affiliations

  • R. H. Scheuermann
    • 1
  • E. Racila
    • 2
  • J. W. Uhr
    • 2
  1. 1.Laboratory of Molecular Pathology and Department of PathologyUniversity of Texas Southwestern Medical CenterDallasUSA
  2. 2.Department of MicrobiologyUniversity of Texas Southwestern Medical CenterDallasUSA

Personalised recommendations