title: Interleukin-4-mediated aggregation of anti-IgM-stimulated human B cells: inhibition of aggregation but enhancement of proliferation by antibodies to LFA-1.
abstract: Direct cellular interactions, involving adhesion structures like lymphocyte function-associated antigen-1 (LFA-1) and intercellular adhesion molecule-1 (ICAM-1), play a critical role in the initial stages of T-cell-dependent B-cell activation. However, the relevance of cellular contact in later, lymphokine driven stages of B-cell stimulation is less well understood. We have here studied the ability of different lymphokines [interleukin (IL)-1 alpha, IL-1 beta, IL-2, IL-3, IL-4, IL-6 and interferon-gamma (IFN-gamma)] to stimulate adhesion processes as well as proliferation of highly purified tonsillar B lymphocytes. None of the lymphokines were by themselves able to induce aggregation in resting B cells but, when added together with anti-IgM, IL-4 and to a lesser extent IL-2, promoted the formation of large, dense aggregates which were macroscopically visible after 3-4 days in culture. Addition of anti-LFA-1 antibodies (anti-CD11a or CD18) completely inhibited the lymphokine-promoted aggregation, indicating that cluster formation was mediated by LFA-1. Fluorescence-activated cell sorter (FACS) analysis showed that the expression of both LFA-1 and ICAM-1 increased after stimulation with IL-4 as well as with IFN-gamma. However, in contrast to IL-4, IFN-gamma did not enhance cellular aggregation, suggesting that qualitative rather than quantitative changes in LFA-1/ICAM-1 promote aggregation. Although anti-LFA-1 antibodies inhibited aggregation of both IL-2- and IL-4-stimulated cells they did not inhibit proliferation. In contrast, in IL-4-stimulated cultures inhibition of cell contact resulted in a significantly increased proliferation. Furthermore, IFN-gamma-stimulated cells responded with proliferation in the absence of aggregation. Taken together, the findings suggest that LFA-1-dependent cellular contact plays a minor role in lymphokine driven B-cell proliferation. The possible importance of aggregation in B-cell differentiation is discussed.
authors.affiliation: Department of Immunology, Stockholm University, Sweden.
authors.forename: P
authors.initials: P
authors.lastname: Björck
authors.forename: S
authors.initials: S
authors.lastname: Paulie
authors.forename: B
authors.initials: B
authors.lastname: Axelsson
mesh_terms: D000888:Antibodies, Anti-Idiotypic / Q000276:immunology*; D015703:Antigens, CD / Q000032:analysis; D001402:B-Lymphocytes / Q000276:immunology*; D002449:Cell Aggregation / Q000276:immunology; D002455:Cell Division / Q000276:immunology; D002478:Cells, Cultured; D006801:Humans; D007075:Immunoglobulin M / Q000276:immunology*; D015847:Interleukin-4 / Q000276:immunology*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000276:immunology*; D008222:Lymphokines / Q000276:immunology; D011994:Recombinant Proteins / Q000276:immunology
chemical_list: D000888:Antibodies, Anti-Idiotypic; D015703:Antigens, CD; D007075:Immunoglobulin M; D016169:Lymphocyte Function-Associated Antigen-1; D008222:Lymphokines; D011994:Recombinant Proteins; D015847:Interleukin-4