title: Lymphotoxin α1β2 expression on B cells is required for follicular dendritic cell activation during the germinal center response.
abstract: CD19-deficient mice were used as a model to study follicular dendritic cell (FDC) activation because these mice have normal numbers of FDC-containing primary follicles, but lack the ability to activate FDCs or form GCs. It was hypothesized that CD19 expression is necessary for B-cell activation and upregulation of membrane lymphotoxin (mLT) expression, which promotes FDC activation. Using VCAM-1 and FcγRII/III as FDC activation markers, it was determined that the adoptive transfer of CD19(+)  wild-type B cells into CD19-deficient hosts rescued GC formation and FDC activation, demonstrating that CD19 expression on B cells is required for FDC activation. In contrast, CD19(+)  donor B cells lacking mLT were unable to induce VCAM-1 expression on FDCs, furthermore FcγRII/III upregulation was impaired in FDCs stimulated with mLT-deficient B cells. VCAM-1 expression on FDCs, but not FcγRII/III, was rescued when CD19-deficient B cells expressing transgenic mLT were cotransferred into recipient mice with CD19(+) , mLT-deficient B cells, suggesting that FDC activation requires the CD19-dependent upregulation of mLT on activated B cells. Collectively, these data demonstrate that activated B cells are responsible for the initiation of FDC activation resulting in a microenvironment supportive of GC development and maintenance.
authors.affiliation: Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
authors.forename: Riley C
authors.initials: RC
authors.lastname: Myers
authors.forename: R Glenn
authors.initials: RG
authors.lastname: King
authors.forename: Robert H
authors.initials: RH
authors.lastname: Carter
authors.forename: Louis B
authors.initials: LB
authors.lastname: Justement
mesh_terms: D000818:Animals; D018941:Antigens, CD19 / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D020566:Dendritic Cells, Follicular / Q000276:immunology* / Q000378:metabolism*; D018858:Germinal Center / Q000276:immunology* / Q000378:metabolism*; D008213:Lymphocyte Activation; D053361:Lymphotoxin alpha1, beta2 Heterotrimer / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D017452:Receptors, IgG / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D015854:Up-Regulation; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology
chemical_list: D018941:Antigens, CD19; D053361:Lymphotoxin alpha1, beta2 Heterotrimer; D017452:Receptors, IgG; D019010:Vascular Cell Adhesion Molecule-1