title: Cell clustering and delay/arrest in T-cell division implicate a novel mechanism of immune modulation by E. coli heat-labile enterotoxin B-subunits.
abstract: The B-subunits of heat-labile enterotoxins LT-I (LT-IB) and LT-IIa (LT-IIaB) are strong adjuvants that bind to cell-surface receptors, including gangliosides G(M1) and GD1b, respectively. LT-IIaB also binds TLR-2. We demonstrate for the first time that co-incubation with the B-subunits induces significant clustering of B cells after only 4h, and B and T cells in 24h. Clustering was dependent on intact B-subunits, but not on the TLR-2 binding activity of LT-IIaB, indicating it was ganglioside-mediated. Treatment of B cells with LT-IB, a mixture of LT-IB+LT-IIaB, but not LT-IIaB alone, caused a delay in T cell division following ovalbumin endocytosis. B cell receptor-mediated uptake in presence of each treatment caused an arrest, but with increased production of IL-2. Further, treatments differentially increased the proportion of macrophages expressing MHC class-II. These results highlight the outcomes of interplay between signals involving different receptors and implicate a novel mechanism of adjuvanticity.
authors.affiliation: College of Veterinary Medicine, Nursing & Allied Health, Department of Pathobiology, Tuskegee University, 1200 Montgomery Road, Tuskegee, AL 36088, USA; Kafrelshikh University, College of Veterinary Medicine, Kafrelsheikh, Egypt.
authors.forename: Seham
authors.initials: S
authors.lastname: El-Kassas
authors.affiliation: College of Veterinary Medicine, Nursing & Allied Health, Department of Pathobiology, Tuskegee University, 1200 Montgomery Road, Tuskegee, AL 36088, USA; Middle Technical University, Institute of Medical Technology, Department of Community Health, Baghdad, Iraq.
authors.forename: Rawah
authors.initials: R
authors.lastname: Faraj
authors.affiliation: College of Veterinary Medicine, Nursing & Allied Health, Department of Pathobiology, Tuskegee University, 1200 Montgomery Road, Tuskegee, AL 36088, USA.
authors.forename: Karmarcha
authors.initials: K
authors.lastname: Martin
authors.affiliation: Pennsylvania School of Dental Medicine, Department of Microbiology, Philadelphia, PA 19104, USA.
authors.forename: George
authors.initials: G
authors.lastname: Hajishengallis
authors.affiliation: The Department of Microbiology & Immunology and The Witebsky Center for Microbial Pathogenesis and Immunology, School of Medicine and Biomedical Sciences, 138 Farber Hall, 3435 Main St., University at Buffalo, NY 14214, USA.
authors.forename: Terry D
authors.initials: TD
authors.lastname: Connell
authors.affiliation: College of Veterinary Medicine, Nursing & Allied Health, Department of Pathobiology, Tuskegee University, 1200 Montgomery Road, Tuskegee, AL 36088, USA. Electronic address: tnashar@mytu.tuskegee.edu.
authors.forename: Toufic
authors.initials: T
authors.lastname: Nashar
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D001427:Bacterial Toxins / Q000276:immunology*; D002453:Cell Cycle / Q000276:immunology; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004768:Enterotoxins / Q000276:immunology*; D029968:Escherichia coli Proteins / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D007376:Interleukin-2 / Q000276:immunology; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D051379:Mice; D010047:Ovalbumin / Q000276:immunology*; D011956:Receptors, Cell Surface / Q000276:immunology*; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D001427:Bacterial Toxins; D004768:Enterotoxins; D029968:Escherichia coli Proteins; D000949:Histocompatibility Antigens Class II; D007376:Interleukin-2; D011956:Receptors, Cell Surface; D010047:Ovalbumin; C027538:heat-labile enterotoxin, E coli
keywords: Adjuvant; B cells; Enterotoxins; GD1; GM1; Gangliosides; T cells; TLR-2; Vaccine