title: Follicular dendritic cells in aging, a "bottle-neck" in the humoral immune response.
abstract: Senescence leads to the appearance of atrophic follicular dendritic cells (FDCs) that trap and retain little immune complexes (IC), generate few memory B cells, and induce a reduced number of germinal centers (GC). Deficiencies in antibody responses to T cell dependent exogenous antigens such as pneumonia and influenza vaccines may reflect intrinsic FDC defects or altered FDC-B cell interactions. We recently studied antigen handling capacity and co-stimulatory activity of old FDCs and determined age-related changes in the expression or function of FcgammaRII or CR1 and 2 on FDCs. Here, we present an overview of FDC function in recall responses with known deficiencies in FDCs and GC development. Then, we review our recent work on aged FDCs and discuss age-related changes in molecular interactions between FDCs and B cells. We also discuss the causes underlying the impaired humoral immune response with respect to age-related molecular changes in FDC and B cell interactions. In vitro evidence suggests that FcgammaRII on aged FDCs is regulated abnormally and this in turn might cause the development of a defective FDC-network (reticulum) that retains few ICs, promotes ITIM signaling, prevents B cell proliferation and GC formation, and antibody production.
authors.affiliation: Department of Anatomy and Neurobiology, The Immunology Group, Virginia Commonwealth University, Medical College of Virginia Campus, 1101 East Marshall Street, Richmond, VA 23298, USA.
authors.forename: Yüksel
authors.initials: Y
authors.lastname: Aydar
authors.forename: Péter
authors.initials: P
authors.lastname: Balogh
authors.forename: John G
authors.initials: JG
authors.lastname: Tew
authors.forename: Andras K
authors.initials: AK
authors.lastname: Szakal
mesh_terms: D000375:Aging / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D000818:Animals; D000917:Antibody Formation / Q000502:physiology*; D016922:Cellular Senescence / Q000276:immunology; D020566:Dendritic Cells, Follicular / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D006801:Humans