title: Activated T cells can induce high levels of CTLA-4 expression on B cells.
abstract: Engagement of the TCR/CD3 complex together with ligation of CD28 by its counterstructures B7-1 (CD80) and B7-2 (CD86) on APC are required for mitogenic T cell activation. After activation, T cells not only express B7-1 and B7-2 molecules, but a second receptor for the B7 ligands, CTLA-4, can be found on their surfaces. We here show that B cells can be induced to express CTLA-4 on the plasma membrane. Similar to what has been reported for T cells, CTLA-4 expression on B cells was transient. Purified B cells did not express CTLA-4 when mitogenically activated with alpha IgM and CD40 Ab, but did express the molecule when cultured in the presence of membranes from activated T cells, which suggests that induction of CTLA-4 expression on B cells was dependent on direct cell-cell contact of B lymphocytes and activated T cells. CTLA-4 molecules isolated from either T or B cells were biochemically indistinguishable. Moreover, because the ability of chimeric B7-1/Ig proteins to bind to activated B cells was correlated with CTLA-4 expression levels on these cells, we conclude that B cell-expressed CTLA-4 has ligand binding capacity. These data suggest that costimulatory receptors and their specific ligands not only play a role in T cell stimulation, but contribute in a direct fashion to the regulation of B cell responses.
authors.affiliation: Central Laboratory, The Netherlands Red Cross Blood Transfusion Service, Amsterdam.
authors.forename: H M
authors.initials: HM
authors.lastname: Kuiper
authors.forename: M
authors.initials: M
authors.lastname: Brouwer
authors.forename: P S
authors.initials: PS
authors.lastname: Linsley
authors.forename: R A
authors.initials: RA
authors.lastname: van Lier
mesh_terms: D000069594:Abatacept; D000818:Animals; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000096:biosynthesis*; D001402:B-Lymphocytes / Q000276:immunology*; D018122:B7-1 Antigen / Q000502:physiology; D018106:CD28 Antigens / Q000502:physiology; D060908:CTLA-4 Antigen; D002478:Cells, Cultured; D006801:Humans; D018796:Immunoconjugates; D008213:Lymphocyte Activation; D051379:Mice; D013601:T-Lymphocytes / Q000502:physiology*
chemical_list: D015703:Antigens, CD; D000943:Antigens, Differentiation; D018122:B7-1 Antigen; D018106:CD28 Antigens; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; C556707:Ctla4 protein, mouse; D018796:Immunoconjugates; D000069594:Abatacept