title: Impaired uptake of apoptotic cells into tingible body macrophages in germinal centers of patients with systemic lupus erythematosus.
abstract: OBJECTIVE
  To investigate the fate of apoptotic cells in the germinal centers (GCs) of patients with systemic lupus erythematosus (SLE).
  
  
  METHODS
  Lymph node biopsy specimens obtained from 7 SLE patients with benign follicular hyperplasia, 5 non-SLE patients with benign follicular hyperplasia (non-SLE), 5 patients with malignant follicular lymphoma, and 3 patients with dermatopathic lymphadenitis were stained with monoclonal antibodies against macrophages (CD68) and follicular dendritic cells (CR2/CD21). TUNEL staining and transmission electron microscopy were performed to detect apoptotic cells. Confocal microscopy was used to evaluate the in vivo capacity of tingible body macrophages to remove apoptotic cell material.
  
  
  RESULTS
  In a subgroup of patients with SLE, apoptotic cells accumulated in the GCs of the lymph nodes. The number of tingible body macrophages, which usually contained engulfed apoptotic nuclei, was significantly reduced in these patients. In contrast to what was observed in all controls, TUNEL-positive apoptotic material from SLE patients was observed to be directly associated with the surfaces of follicular dendritic cells (FDCs).
  
  
  CONCLUSIONS
  Our findings suggest that in a sub-group of SLE patients, apoptotic cells are not properly cleared by tingible body macrophages of the GCs. Consequently, nuclear autoantigens bind to FDCs and may thus provide survival signals for autoreactive B cells. This action may override an important control mechanism for B cell development, resulting in the loss of tolerance for nuclear antigens.
authors.affiliation: Friedrich-Alexander-University of Erlangen-Nuremberg, Erlangen, Germany.
authors.forename: Irith
authors.initials: I
authors.lastname: Baumann
authors.forename: Wasilis
authors.initials: W
authors.lastname: Kolowos
authors.forename: Reinhard E
authors.initials: RE
authors.lastname: Voll
authors.forename: Bernhard
authors.initials: B
authors.lastname: Manger
authors.forename: Udo
authors.initials: U
authors.lastname: Gaipl
authors.forename: Winfried L
authors.initials: WL
authors.lastname: Neuhuber
authors.forename: Thomas
authors.initials: T
authors.lastname: Kirchner
authors.forename: Joachim R
authors.initials: JR
authors.lastname: Kalden
authors.forename: Martin
authors.initials: M
authors.lastname: Herrmann
mesh_terms: D017209:Apoptosis / Q000502:physiology*; D001706:Biopsy; D002467:Cell Nucleus / Q000473:pathology; D020566:Dendritic Cells, Follicular / Q000737:chemistry / Q000473:pathology; D018858:Germinal Center / Q000473:pathology*; D006801:Humans; D020287:In Situ Nick-End Labeling; D008180:Lupus Erythematosus, Systemic / Q000473:pathology*; D008264:Macrophages / Q000473:pathology*; D018613:Microscopy, Confocal; D010587:Phagocytosis / Q000276:immunology; D017464:Receptors, Complement 3d / Q000032:analysis
chemical_list: D017464:Receptors, Complement 3d