CD44 and Other Cell Interaction Molecules Contributing to B Lymphopoiesis

  • P. W. Kincade
  • Q. He
  • K. Ishihara
  • K. Miyake
  • J. Lesley
  • R. Hyman
Part of the Current Topics in Microbiology and Immunology book series (CT MICROBIOLOGY, volume 184)


The term “adhesion” seems much too narrow to describe the multifunctional molecules on which this book is based. In addition to mediating physical interactions, as the name suggests, they serve as receptors for cell-cell communication and in the binding of cells to the extracellular matrix. The distinction between cell adhesion molecules and growth factor receptors has become blurred by reports that the latter can immobilize cells. Moreover, the same, or closely related, molecules can serve different specialized functions in multiple tissues. Information is gradually accumulating about interaction molecules expressed in lymphohematopoietic tissues and to date none have been convincingly described which are restricted to those sites. Our experience with B lymphocyte precursors suggests that molecules critical for the formation and export of blood cells from bone marrow are closely related to those responsible for their recruitment from the bloodstream and migration within peripheral tissues. Like other cell adhesion molecules, they have the very interesting property of having multiple functional states, which are actively regulated by cells that express them. The emphasis of this review will be on studies which have implicated four cell adhesion/ interaction molecules in B lymphopoiesis.


Stromal Cell Hyaluronic Acid Bone Marrow Stromal Cell Neural Cell Adhesion Molecule Murine Bone Marrow 
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. Aruffo A, Stamenkovic I, Melnick M, Underhill CB, Seed B (1990) CD44 is the principal cell surface receptor for hyaluronate. Cell 61: 1303–1313PubMedCrossRefGoogle Scholar
  2. Bourguignon LYW, Lokeshwar VB, He J, Chen X, Bourguignon GJ (1992) A CD44-like endothelial cell transmembrane glycoprotein (GP116) interacts with extracellular matrix and ankyrin. Mol Cell Biol 12: 4464–4471PubMedGoogle Scholar
  3. Camp RL, Kraus TA, Pure E (1991) Variations in the cytoskeletal interaction and posttranslational modification of the CD44 homing receptor in macrophages. J Cell Biol 115: 1283–1292PubMedCrossRefGoogle Scholar
  4. Cunningham BA, Hemperly JJ, Murray BA, Prediger EA, Brackenbury R, Edelman GM (1987) Neural cell adhesion molecule: structure, immunoglobulin-like domains, cell surface modulation, and alternative RNA splicing. Science 236: 799–806PubMedCrossRefGoogle Scholar
  5. Dustin M L, Springer TA (1989) T-cell receptor cross-linking transiently stimulates adhesiveness through LFA-1. Nature 341: 619–624PubMedCrossRefGoogle Scholar
  6. Faassen AE, Schrager JA, Klein DJ, Oegema TR, Couchman JR, McCarthy JB (1992) A cell surface chondroitin sulfate proteoglycan, immunologically related to CD44, is involved in type I collagen-mediated melanoma cell motility and invasion. J Cell Biol 116: 521–531PubMedCrossRefGoogle Scholar
  7. Gimble JM, Pietrangeli CE, Henley A et al. (1989) Characterization of murine bone marrow and spleen derived stromal cells: analysis of leukocyte marker and growth factor mRNA transcript levels. Blood 74: 303–311PubMedGoogle Scholar
  8. Goldstein LA, Zhou DFH, Picker LJ et al. (1989) A human lymphocyte homing receptor, the hermes antigen, is related to cartilage proteoglycan core and link proteins. Cell 56: 1063–1072PubMedCrossRefGoogle Scholar
  9. Gunthert U, Hofmann M, Rudy W et al. (1991) A new variant of Glycoprotein CD44 confers metastatic potential to rat carcinoma cells. Cell 65: 13–24PubMedCrossRefGoogle Scholar
  10. He Q, Lesley J, Hyman R, Ishihara K, Kincade PW (1992) Molecular isoforms of murine CD44 and evidence that the membrane proximal domain is not critical for hyaluronate recognition. J Cell Biol (in press)Google Scholar
  11. Hession C, Moy P, Tizard R et al. (1992) Cloning of murine and rat vascular cell adhesion molecule-1. Biochem Biophys Res Commun 183: 163–169PubMedCrossRefGoogle Scholar
  12. Hyman R, Lesley J, Schulte R (1991) Somatic cell mutants distinguish CD44 expression and hyaluronic acid binding. Immunogenetics 33: 392–395PubMedCrossRefGoogle Scholar
  13. Hynes RO (1992) Integrins: versatility, modulation, and signaling in cell adhesion. Cell 69: 11–25PubMedCrossRefGoogle Scholar
  14. Ishihara K, Medina K, Hayashi S-l et al. (1991) Stromal-cell and cytokine-dependent lymphocyte clones which span the Pre-B to B-cell transition. Dev Immunol 1: 149–161PubMedCrossRefGoogle Scholar
  15. Jacobsen K, Osmond DG (1990) Microenvironmental organization and stromal cell associations of B lymphocyte precursor cells in mouse bone marrow. Eur J Immunol 20: 2395–2404PubMedCrossRefGoogle Scholar
  16. Jalkanen S, Jalkanen M (1992) Lymphocyte CD44 binds the COOH-terminal heparin-binding domain of fibronectin. J Cell Biol 116: 817–825PubMedCrossRefGoogle Scholar
  17. Kimura K, Matsubara H, Sogoh S et al. (1991) Role of glycosaminoglycans in the regulation of T cell proliferation induced by thymic stroma-derived T cell growth factor. J Immunol 146: 2618–2624PubMedGoogle Scholar
  18. Kincade PW, Lee G, Pietrangeli CE, Hayashi S-l, Gimble JM (1988) Cells and molecules that regulate B lymphopoiesis in bone marrow. Annu Rev Immunol 7: 111–143CrossRefGoogle Scholar
  19. Kincade PW, Medina K, Pietrangeli CE, Hayashi S-l, Namen AE (1991) Stromal cell lines which support lymphocyte growth. II. Characteristics of a suppressive subclone. Adv Exp Med Biol 292: 227–234Google Scholar
  20. Kirchhofer D, Grzesiak J, Pierschbacher MD (1991) Calcium as a potential physiological regulator of integrin-mediated cell adhesion. J Biol Chem 266: 4471–4477PubMedGoogle Scholar
  21. Lee G, Namen AE, Gillis S, Ellingsworth LR, Kincade PW (1989) Normal B cell precursors responsive to recombinant murine IL-7 and inhibition of IL-7 activity by transforming growth factor. J Immunol 142: 3875–3883PubMedGoogle Scholar
  22. Lesley J, Hyman R (1992) CD44 can be activated to function as an hyaluronic acid receptor in normal murine T cells. Eur J Immunol 22: 2719–2723PubMedCrossRefGoogle Scholar
  23. Lesley J, Schulte R, Hyman R (1990) Binding of hyaluronic acid to lymphoid cell lines is inhibited by monoclonal antibodies against Pgp-1. Exp Cell Res 187: 224–233PubMedCrossRefGoogle Scholar
  24. Lesley J, He Q, Miyake K, Hamann A, Hyman R, Kincade PW (1992a) Requirements for hyaluronic acid binding by CD44: a role for the cytoplasmic domain and activation by antibody. J Exp Med 175: 257–266PubMedCrossRefGoogle Scholar
  25. Lesley J, Kincade PW, Hyman R (1992b) Antibody activation of the hyaluronic acid receptor function of CD44 requires multivalent binding by antibody but not signal transduction (submitted for publication)Google Scholar
  26. Miyake K, Kincade PW (1990) A new cell adhesion mechanism involving hyaluronate and CD44. In: Potter M, Melchers F (eds) Mechanisms in B-cell neoplasia 1990. Springer, Berlin Heidelberg New York, pp87–90 (Current topics in microbiology and immunology, vol 166 )Google Scholar
  27. Miyake K, Medina KL, Hayashi S-l, Ono S, Hamaoka T, Kincade PW (1990a) Monoclonal antibodies to Pgp-1/CD44 block lympho-hemopoiesis in long-term bone marrow cultures. J Exp Med 171: 477–488PubMedCrossRefGoogle Scholar
  28. Miyake K, Underhill CB, Lesley J, Kincade PW (1990b) Hyaluronate can function as a cell adhesion molecule and CD44 participates in hyaluronate recognition. J Exp Med 172: 69–75PubMedCrossRefGoogle Scholar
  29. Miyake K, Medina K, Ishihara K, Kimoto M, Auerbach R, Kincade PW (1991a) A VCAM-like adhesion molecule on murine bone marrow stromal cells mediates binding of lymphocyte precursors in culture. J Cell Biol 114: 557–565PubMedCrossRefGoogle Scholar
  30. Miyake K, Weissman IL, Greenberger JS, Kincade PW (1991b) Evidence for a role of the integrin VLA-4 in lympho-hemopoiesis. J Exp Med 173: 599–607PubMedCrossRefGoogle Scholar
  31. Murakami S, Miyake K, June CH, Kincade PW, Hodes RJ (1990) IL-5 induces a Pgp-1 (CD44) bright B cell subpopulation that is highly enriched in proliferative and Ig secretory activity and binds to hyaluronate. J Immunol 145: 3618–3627PubMedGoogle Scholar
  32. Murakami S, Miyake K, Abe R, Kincade PW, Hodes RJ (1991) Characterization of autoantibody- secreting B cells in mice undergoing stimulatory (chronic) graft-versus-host reactions. Identification of a CD44hl population that binds specifically to hyaluronate. J Immunol 146: 1422–1427PubMedGoogle Scholar
  33. Namen AE, Lupton S, Hjerrild K et al. (1988) Stimulation of B-cell progenitors by cloned murine interleukin-7. Nature 333: 571–573PubMedCrossRefGoogle Scholar
  34. O’Toole TE, Loftus JC, Du X et al. (1990) Affinity modulation of the alpha lib beta 3 integrin (platelet GPIIb-IIIa) is an intrinsic property of the receptor. Cell Regul 1: 883–893PubMedGoogle Scholar
  35. Osmond DG, Kim N, Manoukian R, Phillips RA, Rico-Vargas SA, Jacobsen K (1992) Dynamics and localization of early B-lymphocyte precursor cells ( Pro-B cells) in the bone marrow of seid mice. Blood 79: 1695–1703Google Scholar
  36. Pietrangeli CE, Hayashi S-l, Kincade PW (1988) Stromal cell lines which support lymphocyte growth: Characterization, sensitivity to radiation and responsiveness to growth factors. Eur J Immunol 18: 863–872Google Scholar
  37. Rajewsky K (1992) Early and late B-cell development in the mouse. Curr Opin Immunol 4: 171–176PubMedCrossRefGoogle Scholar
  38. Rolink A, Kudo A, Karasuyama H, Kikuchi Y, Melchers F (1991) Long-term proliferating early pre B cell lines and clones with the potential to develop to surface lg-positive, mitogen reactive B cells in vitro and in vivo. EMBO J 10: 327–336PubMedGoogle Scholar
  39. Ryan DH, Nuccie BL, Abboud CN, Winslow JM (1991) Vascular cell adhesion molecule-1 and the integrin VLA-4 mediate adhesion and human B cell precursors to cultured bone marrow adherent cells. J Clin Invest 88: 995–1004PubMedCrossRefGoogle Scholar
  40. Simmons PJ, Masinovsky B, Longenecker BM, Berenson R, Torok-Storb B, Gallatin WM (1992) Vascular cell adhesion molecule-1 expressed by bone marrow stromal cells mediates the binding of hematopoietic progenitor cells. Blood 80: 388–395PubMedGoogle Scholar
  41. Stamenkovic I, Aruffo A, Amiot M, Seed B (1991) The hematopoietic and epithelial forms of CD44 are distinct polypeptides with different adhesion potentials for hyaluronate-bearing cells. EMBO J 10: 343–348PubMedGoogle Scholar
  42. Thomas PS, Pietrangeli CE, Hayashi S-l et al. (1988) Demonstration of neural cell adhesion molecules on stromal cells which support lymphopoiesis. Leukemia 2: 171–175PubMedGoogle Scholar
  43. Whitlock C, Denis K, Robertson D, Witte O (1985) In vitro analysis of murine B-cell development. Annu Rev Immunol 3: 213–235Google Scholar
  44. Witte PL, Robinson M, Henley A et al. (1987) Relationships between B-lineage lymphocytes and stromal cells in long term bone marrow cultures. Eur J Immunol 17: 1473–1484PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin · Heidelberg 1993

Authors and Affiliations

  • P. W. Kincade
    • 1
  • Q. He
    • 1
  • K. Ishihara
    • 1
  • K. Miyake
    • 1
  • J. Lesley
    • 2
  • R. Hyman
    • 2
  1. 1.Immunobiology & Cancer ProgramOklahoma Medical Research FoundationOklahoma CityUSA
  2. 2.Department of Cancer BiologyThe Salk InstituteSan DiegoUSA

Personalised recommendations