title: In vivo expression of B7-1 and B7-2 by follicular lymphoma cells can prevent induction of T-cell anergy but is insufficient to induce significant T-cell proliferation.
abstract: Expression of B7 family costimulatory molecules on B cells defines their capacity to function as antigen presenting cells (APCs). B cells that do not express B7 costimulatory molecules induce T-cell tolerance. Therefore, the expression of B7 costimulatory molecules on malignant B cells might be critical for their recognition by anti-tumor-specific T cells. Here we show that virtually all germinal center (GC)-derived B-cell lymphomas including follicular lymphoma (FL) and diffuse large cell lymphoma, but not mantle cell lymphoma or small lymphocytic lymphomas (SLL/CLL), express B7-1 (CD80) and B7-2 (CD86) on their cell surface in situ, although at extremely low levels. Despite their expression of low levels of B7-1 and B7-2, FL cells could not induce significant allogeneic T-cell proliferation. However, B7 costimulatory molecules on FL appeared to be functional because they were capable of increasing T-cell proliferation of preactivated T cells in a secondary allogeneic mixed lymphocyte response. Moreover, low B7 expression was sufficient to prevent the induction of alloantigen-specific anergy in vitro. Therefore, we postulate that whereas low-level expression of B7 is not sufficient to initiate a productive antilymphoma T-cell response, it might be sufficient to prevent T-cell tolerance in vivo.
authors.affiliation: Department of Pathology, Brigham and Women's Hospital, Boston, MA.
authors.forename: D M
authors.initials: DM
authors.lastname: Dorfman
authors.forename: J L
authors.initials: JL
authors.lastname: Schultze
authors.forename: A
authors.initials: A
authors.lastname: Shahsafaei
authors.forename: S
authors.initials: S
authors.lastname: Michalak
authors.forename: J G
authors.initials: JG
authors.lastname: Gribben
authors.forename: G J
authors.initials: GJ
authors.lastname: Freeman
authors.forename: G S
authors.initials: GS
authors.lastname: Pinkus
authors.forename: L M
authors.initials: LM
authors.lastname: Nadler
mesh_terms: D015703:Antigens, CD / Q000378:metabolism*; D018122:B7-1 Antigen / Q000378:metabolism*; D051940:B7-2 Antigen; D002455:Cell Division; D017635:Clonal Anergy; D006801:Humans; D007124:Immunoenzyme Techniques; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000378:metabolism; D007959:Lymphocyte Culture Test, Mixed; D016393:Lymphoma, B-Cell / Q000378:metabolism; D008224:Lymphoma, Follicular / Q000378:metabolism*; D016403:Lymphoma, Large B-Cell, Diffuse / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism
chemical_list: D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; C497964:CD86 protein, human; D008562:Membrane Glycoproteins