title: Persistent autoantibody-production by intermediates between short-and long-lived plasma cells in inflamed lymph nodes of experimental epidermolysis bullosa acquisita.
abstract: Autoantibodies are believed to be maintained by either the continuous generation of short-lived plasma cells in secondary lymphoid tissues or by long-lived plasma cells localized in bone marrow and spleen. Here, we show in a mouse model for the autoimmune blistering skin disease epidermolysis bullosa acquisita (EBA) that chronic autoantibody production can also be maintained in inflamed lymph nodes, by plasma cells exhibiting intermediate lifetimes. After EBA induction by immunization with a mCOL7c-GST-fusion protein, antigen-specific plasma cells and CD4 T cells were analyzed. Plasma cells were maintained for months in stable numbers in the draining lymph nodes, but not in spleen and bone marrow. In contrast, localization of mCOL7c-GST -specific CD4 T cells was not restricted to lymph nodes, indicating that availability of T cell help does not limit plasma cell localization to this site. BrdU-incorporation studies indicated that pathogenic mCOL7c- and non-pathogenic GST-specific plasma cells resemble intermediates between short-and long-lived plasma cells with half-lives of about 7 weeks. Immunization with mCOL7c-GST also yielded considerable numbers of plasma cells neither specific for mCOL7c- nor GST. These bystander-activated plasma cells exhibited much shorter half-lives and higher population turnover, suggesting that plasma cell lifetimes were only partly determined by the lymph node environment but also by the mode of activation. These results indicate that inflamed lymph nodes can harbor pathogenic plasma cells exhibiting distinct properties and hence may resemble a so far neglected site for chronic autoantibody production.
authors.affiliation: Institute for Systemic Inflammation Research (ISEF), University of Lübeck, Lübeck, Germany.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Tiburzy
authors.affiliation: Institute for Systemic Inflammation Research (ISEF), University of Lübeck, Lübeck, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Szyska
authors.affiliation: Department of Dermatology, University of Lübeck, Lübeck, Germany.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Iwata
authors.affiliation: Institute of Anatomy, University of Lübeck, Lübeck, Germany.
authors.forename: Navina
authors.initials: N
authors.lastname: Chrobok
authors.affiliation: Institute for Systemic Inflammation Research (ISEF), University of Lübeck, Lübeck, Germany.
authors.forename: Upasana
authors.initials: U
authors.lastname: Kulkarni
authors.affiliation: Department of Dermatology, University of Lübeck, Lübeck, Germany.
authors.forename: Misa
authors.initials: M
authors.lastname: Hirose
authors.affiliation: Department of Dermatology, University of Lübeck, Lübeck, Germany.
authors.forename: Ralf J
authors.initials: RJ
authors.lastname: Ludwig
authors.affiliation: Institute of Anatomy, University of Lübeck, Lübeck, Germany.
authors.forename: Kathrin
authors.initials: K
authors.lastname: Kalies
authors.affiliation: Institute of Anatomy, University of Lübeck, Lübeck, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Westermann
authors.affiliation: Institute for Systemic Inflammation Research (ISEF), University of Lübeck, Lübeck, Germany.
authors.forename: David
authors.initials: D
authors.lastname: Wong
authors.affiliation: Institute for Systemic Inflammation Research (ISEF), University of Lübeck, Lübeck, Germany.
authors.forename: Rudolf Armin
authors.initials: RA
authors.lastname: Manz
mesh_terms: D000818:Animals; D001323:Autoantibodies / Q000096:biosynthesis / Q000097:blood / Q000276:immunology*; D001853:Bone Marrow / Q000276:immunology / Q000378:metabolism; D024143:Collagen Type VII / Q000276:immunology; D004195:Disease Models, Animal; D016107:Epidermolysis Bullosa Acquisita / Q000097:blood / Q000276:immunology* / Q000378:metabolism; D018985:Epitopes, B-Lymphocyte / Q000276:immunology; D008198:Lymph Nodes / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D010950:Plasma Cells / Q000276:immunology* / Q000378:metabolism; D013154:Spleen / Q000276:immunology / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism
chemical_list: D001323:Autoantibodies; D024143:Collagen Type VII; D018985:Epitopes, B-Lymphocyte