Skip to main content
PMC home page
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1991 Dec 1;174(6):1313–1322. doi: 10.1084/jem.174.6.1313

Regulated expression and function of CD11c/CD18 integrin on human B lymphocytes. Relation between attachment to fibrinogen and triggering of proliferation through CD11c/CD18

PMCID: PMC2119051  PMID: 1683891

Abstract

CD11c/CD18 (p150,95) is a beta 2 integrin expressed by myeloid, natural killer and certain lymphoid cells such as some cytotoxic T cell clones and B cell malignancies. We have studied the expression and function of CD11c on resting and activated B lymphocytes. Flow cytometry, immunoprecipitation, and mRNA analyses showed that cell activation with phorbol esters or with a variety of stimuli such as Staphylococcus aureus or anti-mu antibodies in combination with cytokines induced de novo CD11c/CD18 cell surface expression on most B cells while CD11b expression was not affected. Functional analysis of CD11c/CD18 on B cells revealed that it plays a dual role. First, CD11c/CD18 is implicated in B cell proliferation, as demonstrated by the ability of several anti-CD11c monoclonal antibodies to trigger comitogenic signals; and second, the newly expressed CD11c/CD18 mediates B cell binding to fibrinogen. Our data conclusively demonstrate the role of CD11c/CD18 on both B cell activation and adhesion processes.

Full Text

The Full Text of this article is available as a PDF (1.1 MB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Altieri D. C., Bader R., Mannucci P. M., Edgington T. S. Oligospecificity of the cellular adhesion receptor Mac-1 encompasses an inducible recognition specificity for fibrinogen. J Cell Biol. 1988 Nov;107(5):1893–1900. doi: 10.1083/jcb.107.5.1893. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Aman P., Gordon J., Klein G. TPA (12-O-tetradecanoyl-phorbol-13-acetate) activation and differentiation of human peripheral B lymphocytes. Immunology. 1984 Jan;51(1):27–34. [PMC free article] [PubMed] [Google Scholar]
  3. Beekhuizen H., Corsèl-van Tilburg A. J., van Furth R. Characterization of monocyte adherence to human macrovascular and microvascular endothelial cells. J Immunol. 1990 Jul 15;145(2):510–518. [PubMed] [Google Scholar]
  4. Bernabeu C., Carrera A. C., De Landázuri M. O., Sánchez-Madrid F. Interaction between the CD45 antigen and phytohemagglutinin. Inhibitory effect on the lectin-induced T cell proliferation by anti-CD45 monoclonal antibody. Eur J Immunol. 1987 Oct;17(10):1461–1466. doi: 10.1002/eji.1830171012. [DOI] [PubMed] [Google Scholar]
  5. Bohnsack J. F., Cooper N. R. CR2 ligands modulate human B cell activation. J Immunol. 1988 Oct 15;141(8):2569–2576. [PubMed] [Google Scholar]
  6. Boyd A. W., Anderson K. C., Freedman A. S., Fisher D. C., Slaughenhoupt B., Schlossman S. F., Nadler L. M. Studies of in vitro activation and differentiation of human B lymphocytes. I. Phenotypic and functional characterization of the B cell population responding to anti-Ig antibody. J Immunol. 1985 Mar;134(3):1516–1523. [PubMed] [Google Scholar]
  7. Cabañas C., Sanchez-Madrid F., Acevedo A., Bellon T., Fernandez J. M., Larraga V., Bernabeu C. Characterization of a CD11c-reactive monoclonal antibody (HC1/1) obtained by immunizing with phorbol ester differentiated U937 cells. Hybridoma. 1988 Apr;7(2):167–176. doi: 10.1089/hyb.1988.7.167. [DOI] [PubMed] [Google Scholar]
  8. Carrera A. C., Rincón M., Sánchez-Madrid F., López-Botet M., de Landaźuri M. O. Triggering of co-mitogenic signals in T cell proliferation by anti-LFA-1 (CD18, CD11a), LFA-3, and CD7 monoclonal antibodies. J Immunol. 1988 Sep 15;141(6):1919–1924. [PubMed] [Google Scholar]
  9. Cebrián M., Yagüe E., Rincón M., López-Botet M., de Landázuri M. O., Sánchez-Madrid F. Triggering of T cell proliferation through AIM, an activation inducer molecule expressed on activated human lymphocytes. J Exp Med. 1988 Nov 1;168(5):1621–1637. doi: 10.1084/jem.168.5.1621. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Corbi A. L., Miller L. J., O'Connor K., Larson R. S., Springer T. A. cDNA cloning and complete primary structure of the alpha subunit of a leukocyte adhesion glycoprotein, p150,95. EMBO J. 1987 Dec 20;6(13):4023–4028. doi: 10.1002/j.1460-2075.1987.tb02746.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Davis L. S., Oppenheimer-Marks N., Bednarczyk J. L., McIntyre B. W., Lipsky P. E. Fibronectin promotes proliferation of naive and memory T cells by signaling through both the VLA-4 and VLA-5 integrin molecules. J Immunol. 1990 Aug 1;145(3):785–793. [PubMed] [Google Scholar]
  12. De la Hera A., Alvarez-Mon M., Sanchez-Madrid F., Martinez C., Durantez A. Co-expression of Mac-1 and p150,95 on CD5+ B cells. Structural and functional characterization in a human chronic lymphocytic leukemia. Eur J Immunol. 1988 Jul;18(7):1131–1134. doi: 10.1002/eji.1830180725. [DOI] [PubMed] [Google Scholar]
  13. Defrance T., Aubry J. P., Rousset F., Vanbervliet B., Bonnefoy J. Y., Arai N., Takebe Y., Yokota T., Lee F., Arai K. Human recombinant interleukin 4 induces Fc epsilon receptors (CD23) on normal human B lymphocytes. J Exp Med. 1987 Jun 1;165(6):1459–1467. doi: 10.1084/jem.165.6.1459. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Diamond M. S., Staunton D. E., de Fougerolles A. R., Stacker S. A., Garcia-Aguilar J., Hibbs M. L., Springer T. A. ICAM-1 (CD54): a counter-receptor for Mac-1 (CD11b/CD18). J Cell Biol. 1990 Dec;111(6 Pt 2):3129–3139. doi: 10.1083/jcb.111.6.3129. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Ding A., Wright S. D., Nathan C. Activation of mouse peritoneal macrophages by monoclonal antibodies to Mac-1 (complement receptor type 3). J Exp Med. 1987 Mar 1;165(3):733–749. doi: 10.1084/jem.165.3.733. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Dongworth D. W., Gotch F. M., Hildreth J. E., Morris A., McMichael A. J. Effects of monoclonal antibodies to the alpha and beta chains of the human lymphocyte function-associated (H-LFA-1) antigen on T lymphocyte functions. Eur J Immunol. 1985 Sep;15(9):888–892. doi: 10.1002/eji.1830150905. [DOI] [PubMed] [Google Scholar]
  17. Fischer A., Durandy A., Sterkers G., Griscelli C. Role of the LFA-1 molecule in cellular interactions required for antibody production in humans. J Immunol. 1986 May 1;136(9):3198–3203. [PubMed] [Google Scholar]
  18. Freedman A. S., Boyd A. W., Anderson K. C., Fisher D. C., Schlossman S. F., Nadler L. M. B5, a new B cell-restricted activation antigen. J Immunol. 1985 Apr;134(4):2228–2235. [PubMed] [Google Scholar]
  19. Freedman A. S., Freeman G., Whitman J., Segil J., Daley J., Levine H., Nadler L. M. Expression and regulation of CD5 on in vitro activated human B cells. Eur J Immunol. 1989 May;19(5):849–855. doi: 10.1002/eji.1830190511. [DOI] [PubMed] [Google Scholar]
  20. Freudenthal P. S., Steinman R. M. The distinct surface of human blood dendritic cells, as observed after an improved isolation method. Proc Natl Acad Sci U S A. 1990 Oct;87(19):7698–7702. doi: 10.1073/pnas.87.19.7698. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Geppert T. D., Lipsky P. E. Activation of T lymphocytes by immobilized monoclonal antibodies to CD3. Regulatory influences of monoclonal antibodies to additional T cell surface determinants. J Clin Invest. 1988 May;81(5):1497–1505. doi: 10.1172/JCI113481. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Harlan J. M., Killen P. D., Senecal F. M., Schwartz B. R., Yee E. K., Taylor R. F., Beatty P. G., Price T. H., Ochs H. D. The role of neutrophil membrane glycoprotein GP-150 in neutrophil adherence to endothelium in vitro. Blood. 1985 Jul;66(1):167–178. [PubMed] [Google Scholar]
  23. Hatzfeld A., Fischer E., Levesque J. P., Perrin R., Hatzfeld J., Kazatchkine M. D. Binding of C3 and C3dg to the CR2 complement receptor induces growth of an Epstein-Barr virus-positive human B cell line. J Immunol. 1988 Jan 1;140(1):170–175. [PubMed] [Google Scholar]
  24. Hemler M. E. VLA proteins in the integrin family: structures, functions, and their role on leukocytes. Annu Rev Immunol. 1990;8:365–400. doi: 10.1146/annurev.iy.08.040190.002053. [DOI] [PubMed] [Google Scholar]
  25. Hogg N., Takacs L., Palmer D. G., Selvendran Y., Allen C. The p150,95 molecule is a marker of human mononuclear phagocytes: comparison with expression of class II molecules. Eur J Immunol. 1986 Mar;16(3):240–248. doi: 10.1002/eji.1830160306. [DOI] [PubMed] [Google Scholar]
  26. Howard D. R., Eaves A. C., Takei F. Lymphocyte function-associated antigen (LFA-1) is involved in B cell activation. J Immunol. 1986 Jun 1;136(11):4013–4018. [PubMed] [Google Scholar]
  27. Huet S., Groux H., Caillou B., Valentin H., Prieur A. M., Bernard A. CD44 contributes to T cell activation. J Immunol. 1989 Aug 1;143(3):798–801. [PubMed] [Google Scholar]
  28. Keizer G. D., Borst J., Figdor C. G., Spits H., Miedema F., Terhorst C., De Vries J. E. Biochemical and functional characteristics of the human leukocyte membrane antigen family LFA-1, Mo-1 and p150,95. Eur J Immunol. 1985 Nov;15(11):1142–1148. doi: 10.1002/eji.1830151114. [DOI] [PubMed] [Google Scholar]
  29. Keizer G. D., Borst J., Visser W., Schwarting R., de Vries J. E., Figdor C. G. Membrane glycoprotein p150,95 of human cytotoxic T cell clone is involved in conjugate formation with target cells. J Immunol. 1987 May 15;138(10):3130–3136. [PubMed] [Google Scholar]
  30. Kishimoto T. K., O'Connor K., Lee A., Roberts T. M., Springer T. A. Cloning of the beta subunit of the leukocyte adhesion proteins: homology to an extracellular matrix receptor defines a novel supergene family. Cell. 1987 Feb 27;48(4):681–690. doi: 10.1016/0092-8674(87)90246-7. [DOI] [PubMed] [Google Scholar]
  31. Lanier L. L., Arnaout M. A., Schwarting R., Warner N. L., Ross G. D. p150/95, Third member of the LFA-1/CR3 polypeptide family identified by anti-Leu M5 monoclonal antibody. Eur J Immunol. 1985 Jul;15(7):713–718. doi: 10.1002/eji.1830150714. [DOI] [PubMed] [Google Scholar]
  32. Loike J. D., Sodeik B., Cao L., Leucona S., Weitz J. I., Detmers P. A., Wright S. D., Silverstein S. C. CD11c/CD18 on neutrophils recognizes a domain at the N terminus of the A alpha chain of fibrinogen. Proc Natl Acad Sci U S A. 1991 Feb 1;88(3):1044–1048. doi: 10.1073/pnas.88.3.1044. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Luscinskas F. W., Brock A. F., Arnaout M. A., Gimbrone M. A., Jr Endothelial-leukocyte adhesion molecule-1-dependent and leukocyte (CD11/CD18)-dependent mechanisms contribute to polymorphonuclear leukocyte adhesion to cytokine-activated human vascular endothelium. J Immunol. 1989 Apr 1;142(7):2257–2263. [PubMed] [Google Scholar]
  34. Marlin S. D., Springer T. A. Purified intercellular adhesion molecule-1 (ICAM-1) is a ligand for lymphocyte function-associated antigen 1 (LFA-1). Cell. 1987 Dec 4;51(5):813–819. doi: 10.1016/0092-8674(87)90104-8. [DOI] [PubMed] [Google Scholar]
  35. Matsuyama T., Yamada A., Kay J., Yamada K. M., Akiyama S. K., Schlossman S. F., Morimoto C. Activation of CD4 cells by fibronectin and anti-CD3 antibody. A synergistic effect mediated by the VLA-5 fibronectin receptor complex. J Exp Med. 1989 Oct 1;170(4):1133–1148. doi: 10.1084/jem.170.4.1133. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Meuer S. C., Hussey R. E., Fabbi M., Fox D., Acuto O., Fitzgerald K. A., Hodgdon J. C., Protentis J. P., Schlossman S. F., Reinherz E. L. An alternative pathway of T-cell activation: a functional role for the 50 kd T11 sheep erythrocyte receptor protein. Cell. 1984 Apr;36(4):897–906. doi: 10.1016/0092-8674(84)90039-4. [DOI] [PubMed] [Google Scholar]
  37. Micklem K. J., Sim R. B. Isolation of complement-fragment-iC3b-binding proteins by affinity chromatography. The identification of p150,95 as an iC3b-binding protein. Biochem J. 1985 Oct 1;231(1):233–236. doi: 10.1042/bj2310233. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Miller L. J., Schwarting R., Springer T. A. Regulated expression of the Mac-1, LFA-1, p150,95 glycoprotein family during leukocyte differentiation. J Immunol. 1986 Nov 1;137(9):2891–2900. [PubMed] [Google Scholar]
  39. Miller R. A., Gralow J. The induction of Leu-1 antigen expression in human malignant and normal B cells by phorbol myristic acetate (PMA). J Immunol. 1984 Dec;133(6):3408–3414. [PubMed] [Google Scholar]
  40. Nemerow G. R., McNaughton M. E., Cooper N. R. Binding of monoclonal antibody to the Epstein Barr virus (EBV)/CR2 receptor induces activation and differentiation of human B lymphocytes. J Immunol. 1985 Nov;135(5):3068–3073. [PubMed] [Google Scholar]
  41. Parham P., Androlewicz M. J., Brodsky F. M., Holmes N. J., Ways J. P. Monoclonal antibodies: purification, fragmentation and application to structural and functional studies of class I MHC antigens. J Immunol Methods. 1982 Sep 17;53(2):133–173. doi: 10.1016/0022-1759(82)90137-5. [DOI] [PubMed] [Google Scholar]
  42. Plow E. F., Ginsberg M. H. Cellular adhesion: GPIIb-IIIa as a prototypic adhesion receptor. Prog Hemost Thromb. 1989;9:117–156. [PubMed] [Google Scholar]
  43. Ruoslahti E. Integrins. J Clin Invest. 1991 Jan;87(1):1–5. doi: 10.1172/JCI114957. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Sanchez-Madrid F., Nagy J. A., Robbins E., Simon P., Springer T. A. A human leukocyte differentiation antigen family with distinct alpha-subunits and a common beta-subunit: the lymphocyte function-associated antigen (LFA-1), the C3bi complement receptor (OKM1/Mac-1), and the p150,95 molecule. J Exp Med. 1983 Dec 1;158(6):1785–1803. doi: 10.1084/jem.158.6.1785. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Schwarting R., Stein H., Wang C. Y. The monoclonal antibodies alpha S-HCL 1 (alpha Leu-14) and alpha S-HCL 3 (alpha Leu-M5) allow the diagnosis of hairy cell leukemia. Blood. 1985 Apr;65(4):974–983. [PubMed] [Google Scholar]
  46. Shimizu Y., Van Seventer G. A., Siraganian R., Wahl L., Shaw S. Dual role of the CD44 molecule in T cell adhesion and activation. J Immunol. 1989 Oct 15;143(8):2457–2463. [PubMed] [Google Scholar]
  47. Shimizu Y., van Seventer G. A., Horgan K. J., Shaw S. Costimulation of proliferative responses of resting CD4+ T cells by the interaction of VLA-4 and VLA-5 with fibronectin or VLA-6 with laminin. J Immunol. 1990 Jul 1;145(1):59–67. [PubMed] [Google Scholar]
  48. Springer T. A. Adhesion receptors of the immune system. Nature. 1990 Aug 2;346(6283):425–434. doi: 10.1038/346425a0. [DOI] [PubMed] [Google Scholar]
  49. Stacker S. A., Springer T. A. Leukocyte integrin P150,95 (CD11c/CD18) functions as an adhesion molecule binding to a counter-receptor on stimulated endothelium. J Immunol. 1991 Jan 15;146(2):648–655. [PubMed] [Google Scholar]
  50. Sánchez-Madrid F., De Landázuri M. O., Morago G., Cebrián M., Acevedo A., Bernabeu C. VLA-3: a novel polypeptide association within the VLA molecular complex: cell distribution and biochemical characterization. Eur J Immunol. 1986 Nov;16(11):1343–1349. doi: 10.1002/eji.1830161106. [DOI] [PubMed] [Google Scholar]
  51. Thoman M. L., Meuth J. L., Morgan E. L., Weigle W. O., Hugli T. E. C3d-K, a kallikrein cleavage fragment of iC3b is a potent inhibitor of cellular proliferation. J Immunol. 1984 Nov;133(5):2629–2633. [PubMed] [Google Scholar]
  52. Tohma S., Hirohata S., Lipsky P. E. The role of CD11a/CD18-CD54 interactions in human T cell-dependent B cell activation. J Immunol. 1991 Jan 15;146(2):492–499. [PubMed] [Google Scholar]
  53. Torimoto Y., Sugita K., Weinberg D. S., Dang N. H., Donahue C., Letvin N. L., Schlossman S. F., Morimoto C. Development of a monoclonal antibody, anti-6C2, which is involved in the interaction of CD4 T helper cells and activated B cells. J Immunol. 1991 Apr 1;146(7):2176–2184. [PubMed] [Google Scholar]
  54. Tsokos G. C., Lambris J. D., Finkelman F. D., Anastassiou E. D., June C. H. Monovalent ligands of complement receptor 2 inhibit whereas polyvalent ligands enhance anti-Ig-induced human B cell intracytoplasmic free calcium concentration. J Immunol. 1990 Mar 1;144(5):1640–1645. [PubMed] [Google Scholar]
  55. Van Seventer G. A., Shimizu Y., Horgan K. J., Shaw S. The LFA-1 ligand ICAM-1 provides an important costimulatory signal for T cell receptor-mediated activation of resting T cells. J Immunol. 1990 Jun 15;144(12):4579–4586. [PubMed] [Google Scholar]
  56. Wacholtz M. C., Patel S. S., Lipsky P. E. Leukocyte function-associated antigen 1 is an activation molecule for human T cells. J Exp Med. 1989 Aug 1;170(2):431–448. doi: 10.1084/jem.170.2.431. [DOI] [PMC free article] [PubMed] [Google Scholar]
  57. Werb Z., Tremble P. M., Behrendtsen O., Crowley E., Damsky C. H. Signal transduction through the fibronectin receptor induces collagenase and stromelysin gene expression. J Cell Biol. 1989 Aug;109(2):877–889. doi: 10.1083/jcb.109.2.877. [DOI] [PMC free article] [PubMed] [Google Scholar]
  58. Wormsley S. B., Baird S. M., Gadol N., Rai K. R., Sobol R. E. Characteristics of CD11c+CD5+ chronic B-cell leukemias and the identification of novel peripheral blood B-cell subsets with chronic lymphoid leukemia immunophenotypes. Blood. 1990 Jul 1;76(1):123–130. [PubMed] [Google Scholar]
  59. Wright S. D., Reddy P. A., Jong M. T., Erickson B. W. C3bi receptor (complement receptor type 3) recognizes a region of complement protein C3 containing the sequence Arg-Gly-Asp. Proc Natl Acad Sci U S A. 1987 Apr;84(7):1965–1968. doi: 10.1073/pnas.84.7.1965. [DOI] [PMC free article] [PubMed] [Google Scholar]
  60. Wright S. D., Weitz J. I., Huang A. J., Levin S. M., Silverstein S. C., Loike J. D. Complement receptor type three (CD11b/CD18) of human polymorphonuclear leukocytes recognizes fibrinogen. Proc Natl Acad Sci U S A. 1988 Oct;85(20):7734–7738. doi: 10.1073/pnas.85.20.7734. [DOI] [PMC free article] [PubMed] [Google Scholar]
  61. Yamada A., Nikaido T., Nojima Y., Schlossman S. F., Morimoto C. Activation of human CD4 T lymphocytes. Interaction of fibronectin with VLA-5 receptor on CD4 cells induces the AP-1 transcription factor. J Immunol. 1991 Jan 1;146(1):53–56. [PubMed] [Google Scholar]
  62. Yamada A., Nojima Y., Sugita K., Dang N. H., Schlossman S. F., Morimoto C. Cross-linking of VLA/CD29 molecule has a co-mitogenic effect with anti-CD3 on CD4 cell activation in serum-free culture system. Eur J Immunol. 1991 Feb;21(2):319–325. doi: 10.1002/eji.1830210212. [DOI] [PubMed] [Google Scholar]
  63. Yokochi T., Holly R. D., Clark E. A. B lymphoblast antigen (BB-1) expressed on Epstein-Barr virus-activated B cell blasts, B lymphoblastoid cell lines, and Burkitt's lymphomas. J Immunol. 1982 Feb;128(2):823–827. [PubMed] [Google Scholar]
  64. de la Hera A., Acevedo A., Marston W., Sanchez-Madrid F. Function of CD44(Pgp-1) homing receptor in human T cell precursors. Int Immunol. 1989;1(6):598–604. doi: 10.1093/intimm/1.6.598. [DOI] [PubMed] [Google Scholar]
  65. te Velde A. A., Keizer G. D., Figdor C. G. Differential function of LFA-1 family molecules (CD11 and CD18) in adhesion of human monocytes to melanoma and endothelial cells. Immunology. 1987 Jul;61(3):261–267. [PMC free article] [PubMed] [Google Scholar]
  66. van Noesel C., Miedema F., Brouwer M., de Rie M. A., Aarden L. A., van Lier R. A. Regulatory properties of LFA-1 alpha and beta chains in human T-lymphocyte activation. Nature. 1988 Jun 30;333(6176):850–852. doi: 10.1038/333850a0. [DOI] [PubMed] [Google Scholar]

Articles from The Journal of Experimental Medicine are provided here courtesy of The Rockefeller University Press

RESOURCES