title: The CD40 ligand expressed by human B cells costimulates B cell responses.
abstract: The possibility that activated B cells might express a ligand for CD40 that was of functional importance for B cell responses was examined by using highly purified human peripheral blood B cells, as well as a variety of B lymphoblastoid cell lines and hybridomas. Following stimulation with the combination of a calcium ionophore and a phorbol ester, human B cells bound a soluble fusion protein containing the extracellular portion of CD40 and the Fc region of IgG1 (CD40.Ig). A variety of B cell lines and hybridomas also bound CD40.Ig, either constitutively or after activation. In addition, CD40.Ig specifically immunoprecipitated a 33-kDa glycoprotein from surface 125I-labeled activated B cells. The nucleotide sequence of the coding region of the CD40 ligand mRNA amplified by RT-PCR from activated T cells and B cell lines was identical. The CD40 ligand expressed on human B cells was important functionally because homotypic aggregation of CD40 ligand-expressing B cells was inhibited by the CD40.Ig construct. Additionally, RNA and DNA synthesis as well as Ig production by polyclonally activated, highly purified peripheral B cells and a variety of B cell lines were inhibited significantly by the CD40.Ig construct. Finally, B cell lines expressing the CD40 ligand induced Ig production from resting normal B cells in a CD40-dependent manner. These results indicate that human B cells express a ligand for CD40 that is identical with that expressed by activated T cells and that the B cell-expressed CD40 ligand plays an important role in facilitating responses of activated B cells.
authors.affiliation: Immunology Graduate Program, University of Texas Southwestern Medical Center, Dallas 75235, USA.
authors.forename: A C
authors.initials: AC
authors.lastname: Grammer
authors.forename: M C
authors.initials: MC
authors.lastname: Bergman
authors.forename: Y
authors.initials: Y
authors.lastname: Miura
authors.forename: K
authors.initials: K
authors.lastname: Fujita
authors.forename: L S
authors.initials: LS
authors.lastname: Davis
authors.forename: P E
authors.initials: PE
authors.lastname: Lipsky
mesh_terms: D000328:Adult; D015703:Antigens, CD / Q000276:immunology; D000944:Antigens, Differentiation, B-Lymphocyte / Q000276:immunology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D001483:Base Sequence; D019013:CD40 Antigens; D023201:CD40 Ligand; D002460:Cell Line; D004247:DNA / Q000096:biosynthesis; D018076:DNA, Complementary / Q000737:chemistry; D005434:Flow Cytometry; D006801:Humans; D007136:Immunoglobulins / Q000096:biosynthesis; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D008969:Molecular Sequence Data; D011233:Precipitin Tests; D012313:RNA / Q000096:biosynthesis; D015398:Signal Transduction / Q000276:immunology*
chemical_list: D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; D000945:Antigens, Differentiation, T-Lymphocyte; D019013:CD40 Antigens; D018076:DNA, Complementary; D007136:Immunoglobulins; D008562:Membrane Glycoproteins; D023201:CD40 Ligand; D012313:RNA; D004247:DNA