title: Splenic proliferative lymphoid nodules distinct from germinal centers are sites of autoantigen stimulation in immune thrombocytopenia.
abstract: To understand more specific abnormalities of humoral autoimmunity, we studied 31 spleens from immune thrombocytopenia (ITP) patients and 36 control spleens. Detailed analysis identified at least 2 different splenic structures accommodating proliferating B cells, classic germinal centers (GCs), and proliferative lymphoid nodules (PLNs). PLNs were characterized by proliferating Ki67(+) B cells close to follicular dendritic cells (FDCs) and lacked polarization into dark and light zones. As opposed to cells in GCs, proliferating B cells in PLN lacked expression of Bcl6. In both PLNs and GCs of ITP spleens, the density of T cells was significantly reduced. Both T follicular helper cells (T(FH)) and regulatory T cells were reduced within PLNs of ITP spleens suggesting a defect of tolerance related to a loss of T-cell control. Within PLNs of ITP, but not controls, abundant platelet glycoprotein (GP) IIb/IIIa autoantigens was found in IgM containing immune complexes tightly bound to FDCs and closely approximated to proliferating B cells. GPIV was found less often, but not in the same PLNs as GPIIb/IIIa. Autoantigens were not found in the GCs of ITP or controls indicating that PLNs are the sites of autoantigen stimulation in ITP potentially related to a lack of control by T cells and/or the present autoantigen.
authors.affiliation: CC12 Department of Medicine, Rheumatology and Clinical Immunology, Charite´–University Medicine Berlin, Berlin, Germany.
authors.forename: Capucine
authors.initials: C
authors.lastname: Daridon
authors.forename: Christoph
authors.initials: C
authors.lastname: Loddenkemper
authors.forename: Simone
authors.initials: S
authors.lastname: Spieckermann
authors.forename: Anja A
authors.initials: AA
authors.lastname: Kühl
authors.forename: Abdulgabar
authors.initials: A
authors.lastname: Salama
authors.forename: Gerd R
authors.initials: GR
authors.lastname: Burmester
authors.forename: Peter E
authors.initials: PE
authors.lastname: Lipsky
authors.forename: Thomas
authors.initials: T
authors.lastname: Dörner
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001324:Autoantigens / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology / Q000473:pathology*; D049109:Cell Proliferation; D018858:Germinal Center / Q000276:immunology / Q000473:pathology*; D006801:Humans; D019394:Ki-67 Antigen / Q000276:immunology; D008198:Lymph Nodes / Q000276:immunology / Q000473:pathology*; D008875:Middle Aged; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000276:immunology; D016553:Purpura, Thrombocytopenic, Idiopathic / Q000276:immunology / Q000473:pathology*; D013154:Spleen / Q000276:immunology / Q000473:pathology*; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology; D055815:Young Adult
chemical_list: D001324:Autoantigens; D019394:Ki-67 Antigen; D019039:Platelet Glycoprotein GPIIb-IIIa Complex