title: Expression, regulation, and function of B cell-expressed CD154 in germinal centers.
abstract: Activated B cells and T cells express CD154/CD40 ligand in vitro. The in vivo expression and function of B cell CD154 remain unclear and therefore were examined. Tonsillar B and T cells expressed CD154 at a similar density both in situ and immediately ex vivo, whereas a significantly higher percentage of the former expressed CD154. CD154-expressing B cells were most frequent in the CD38positiveIgD+ pre-germinal center (GC)/GC founder, CD38positive GC and CD38-IgD- memory populations, and were also found in the CD38-IgD+ naive and CD38brightIgD+ plasmablast subsets, but not in the CD38brightIgD- plasma cell subset. B cell expression of CD154 was induced by engaging surface Ig or CD40 by signals that predominantly involved activation of AP-1/NF-AT and NF-kappaB, respectively. The functional importance of CD154-mediated homotypic B cell interactions in vivo was indicated by the finding that mAb to CD154 inhibited differentiation of CD38positiveIgD- GC B cells to CD38-IgD- memory cells. In addition, mAb to CD154 inhibited proliferation induced by engaging sIg or CD40, indicating the role of up-regulation of this molecule in facilitating B cell responsiveness. Of note, CD154 itself not only functioned as a ligand but also as a direct signaling molecule as anti-CD154-conjugated Sepharose beads costimulated B cell responses induced by engaging surface Ig. These results indicate that CD154 is expressed by human B cells in vivo and plays an important role in mediating B cell responses.
authors.affiliation: Harold C. Simmons Arthritis Research Center, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas 75235, USA.
authors.forename: A C
authors.initials: AC
authors.lastname: Grammer
authors.forename: R D
authors.initials: RD
authors.lastname: McFarland
authors.forename: J
authors.initials: J
authors.lastname: Heaney
authors.forename: B F
authors.initials: BF
authors.lastname: Darnell
authors.forename: P E
authors.initials: PE
authors.lastname: Lipsky
mesh_terms: D000111:Acetylcysteine / Q000031:analogs & derivatives / Q000494:pharmacology; D016175:B-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism*; D019013:CD40 Antigens / Q000378:metabolism*; D023201:CD40 Ligand; D002450:Cell Communication / Q000276:immunology; D002452:Cell Count; D002469:Cell Separation; D002478:Cells, Cultured; D016572:Cyclosporine / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D018858:Germinal Center / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D006801:Humans; D007156:Immunologic Memory; D016130:Immunophenotyping; D008024:Ligands; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000276:immunology* / Q000378:metabolism; D014066:Palatine Tonsil; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D011947:Receptors, Antigen, B-Cell / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology; D015854:Up-Regulation / Q000276:immunology
chemical_list: D019013:CD40 Antigens; D005419:Flavonoids; D008024:Ligands; D008562:Membrane Glycoproteins; D011500:Protein Synthesis Inhibitors; D011947:Receptors, Antigen, B-Cell; C067713:lactacystin; D023201:CD40 Ligand; D016572:Cyclosporine; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one; D000111:Acetylcysteine