title: Connexin 43 communication channels in follicular dendritic cell development and in follicular lymphomas.
abstract: Follicular dendritic cells (FDC) show homo- and heterocellular metabolic coupling through connexin 43 (Cx43) gap junctions and support B cell selection and maturation in germinal centers. In follicular lymphomas B cells escape apoptosis while FDC develop abnormally. Here we tested Cx43 channels in reactive FDC development and follicular lymphomas. In culture, the treatment of FDC-B cell clusters (resembling to "ex vivo" germinal centers) with Gap27 peptide, mimicking the 2nd extracellular loop of Cx43 protein, significantly impaired FDC-B cell cluster formation and cell survival. In untreated cultures of intact clusters, cell proliferation showed a moderate reduction. In tissues, Cx43 protein levels run parallel with the density of FDC both in reactive germinal centers and in malformed follicles of follicular lymphomas and showed strong upregulation in newly generated and/or degrading bi-/multinuclear FDC of rudimentary processes. However, the inverse correlation between Cx43 expression and B cell proliferation seen in reactive germinal centers was not detected in follicular lymphomas. Furthermore, Cx43 levels were not associated with either lymphoma grade or bone marrow involvement. Our results suggest that Cx43 channels are critical in FDC and "ex vivo" germinal center development and in the persistence of FDC in follicular lymphomas but do not affect tumor progression.
authors: 1st Department of Pathology and Experimental Cancer Research, 1085 Budapest, Hungary.
authors: Hajnalka
authors: H
authors: Rajnai
authors: 1st Department of Pathology and Experimental Cancer Research, 1085 Budapest, Hungary.
authors: Ivett
authors: I
authors: Teleki
authors: 1st Department of Pathology and Experimental Cancer Research, 1085 Budapest, Hungary.
authors: Gergo
authors: G
authors: Kiszner
authors: 1st Department of Pathology and Experimental Cancer Research, 1085 Budapest, Hungary.
authors: Nora
authors: N
authors: Meggyesházi
authors: 1st Department of Pathology and Experimental Cancer Research, 1085 Budapest, Hungary.
authors: Peter
authors: P
authors: Balla
authors: 1st Department of Pathology and Experimental Cancer Research, 1085 Budapest, Hungary.
authors: Tamas
authors: T
authors: Vancsik
authors: 2nd Department of Internal Medicine, 1085 Budapest, Hungary.
authors: Gyorgyi
authors: G
authors: Muzes
authors: 1st Department of Pathology and Experimental Cancer Research, 1085 Budapest, Hungary.
authors: Judit
authors: J
authors: Csomor
authors: 1st Department of Pathology and Experimental Cancer Research, 1085 Budapest, Hungary.
authors: Andras
authors: A
authors: Matolcsy
authors: 1st Department of Pathology and Experimental Cancer Research, 1085 Budapest, Hungary ; MTA-SE Tumor Progression Research Group, 1085 Budapest, Hungary.
authors: Tibor
authors: T
authors: Krenacs
mesh_terms: D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D001853:Bone Marrow / Q000473:pathology; D018031:Connexin 43 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D020566:Dendritic Cells, Follicular / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism*; D015870:Gene Expression; D018858:Germinal Center / Q000276:immunology / Q000378:metabolism; D006801:Humans; D008224:Lymphoma, Follicular / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D010455:Peptides / Q000494:pharmacology; D014407:Tumor Cells, Cultured
chemical_list: D018031:Connexin 43; D010455:Peptides