title: The role of CD11a/CD18-CD54 interactions in human T cell-dependent B cell activation.
abstract: The role of leukocyte function-associated Ag-1 (LFA-1, CD11a/CD18) and intercellular adhesion molecule 1 (ICAM-1, CD54) interactions in human T cell and B cell collaboration was examined by studying the effect of mAb to these determinants on B cell proliferation and differentiation stimulated by culturing resting B cells with CD4+ T cells activated with immobilized mAb to the CD3 molecular complex. In this model system, mAb to either the alpha (CD11a) or beta (CD18) chain of LFA-1 or ICAM-1 (CD54) inhibited B cell responses significantly. The mAb did not directly inhibit B cell function, inasmuch as T cell-independent activation induced by formalinized Staphylococcus aureus and IL-2 was not suppressed. Moreover, DNA synthesis and IL-2 production by immobilized anti-CD3-stimulated CD4+ T cells were not suppressed by the mAb to LFA-1 or ICAM-1. Although the mAb to LFA-1 inhibited enhancement of IL-2 production by co-culture of immobilized anti-CD3-stimulated CD4+ T cells with B cells, addition of exogenous IL-2 or supernatants of mitogen-activated T cells could not abrogate the inhibitory effects of the mAb to LFA-1 or ICAM-1 on B cell responses. Inhibition was most marked when the mAb were present during the initial 24 h in culture. Immobilized anti-CD3-stimulated LFA-1-negative CD4+ T cell clones from a child with leukocyte adhesion deficiency could induce B cell responses, which were inhibited by mAb to LFA-1 or ICAM-1. These results indicate that the interactions between LFA-1 and ICAM-1 play an important role in mediating the collaboration between activated CD4+ T cells and B cells necessary for the induction of B cell proliferation and differentiation, and for enhancement of IL-2 production by CD4+ T cells. Moreover, the data are consistent with a model of T cell-B cell collaboration in which interactions between LFA-1 on resting B cells and ICAM-1 on activated CD4+ T cells play a critical role in initial T cell-dependent B cell activation.
authors.affiliation: Harold C. Simmons Arthritis Research Center, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas 75235.
authors.forename: S
authors.initials: S
authors.lastname: Tohma
authors.forename: S
authors.initials: S
authors.lastname: Hirohata
authors.forename: P E
authors.initials: PE
authors.lastname: Lipsky
mesh_terms: D000328:Adult; D000911:Antibodies, Monoclonal; D015703:Antigens, CD / Q000502:physiology*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000502:physiology; D001402:B-Lymphocytes / Q000276:immunology*; D017252:CD3 Complex; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D015815:Cell Adhesion Molecules / Q000502:physiology*; D002450:Cell Communication / Q000276:immunology; D002454:Cell Differentiation; D002455:Cell Division; D002999:Clone Cells; D006801:Humans; D018799:Intercellular Adhesion Molecule-1; D007376:Interleukin-2 / Q000502:physiology; D007700:Kinetics; D008213:Lymphocyte Activation / Q000276:immunology*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000502:physiology*; D011948:Receptors, Antigen, T-Cell / Q000502:physiology; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D015815:Cell Adhesion Molecules; D007376:Interleukin-2; D016169:Lymphocyte Function-Associated Antigen-1; D011948:Receptors, Antigen, T-Cell; D018799:Intercellular Adhesion Molecule-1