title: Epithelioid germinal centers in overwhelming childhood infections. The aftermath of nonspecific destruction of follicular B cells by natural killer cells.
abstract: The destruction of proliferating lymphoid cells within germinal centers with subsequent replacement by histiocytoid cells has been described in infants and children dying of viral and bacterial infections. The etiology and significance of "epithelioid germinal centers" (EGCs) are unknown. The cells implicated in forming EGCs have included histiocytes and dendritic reticulum cells. We have studied four children at autopsy who died at ages ranging from 10 months to 7 years. Three contracted fatal infections, one with fulminant meningococcemia, one with bacterial sepsis, and one with viral hepatitis. The fourth child contracted viral pneumonitis and died of acetaminophen toxicity. Epithelioid germinal centers were found in numerous lymphoid organs (spleen, lymph nodes, and Peyer's patches) in all four cases. Avidin-biotin complex immunohistochemical analysis performed on formalin-fixed splenic tissue from the first three cases and snap-frozen splenic tissue from the second case revealed an absence of B cells in the follicular centers. The mantle zones surrounding follicles were thin but intact. The histiocytoid cells expanding the germinal centers were positive for S100 and R4/23 (dendritic reticulum cells) and negative for numerous histiocyte markers (alpha 1-antitrypsin, alpha 1-antichymotrypsin, and lysozyme). Increased numbers of killer cells (Leu-7) were present within the affected germinal centers in the three cases in which material was available for immunohistochemical studies. Overwhelming infections in these patients seem to result in anomalous natural killer cell activation resulting in localized nonselective destruction of follicular centers similar to anomalous natural killer cell activity reported to occur in fatal infectious mononucleosis. This may lead to an acquired immunodeficiency that precludes long-term survival in affected patients.
authors.affiliation: Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha 68105.
authors.forename: G S
authors.initials: GS
authors.lastname: Severson
authors.forename: D S
authors.initials: DS
authors.lastname: Harrington
authors.forename: S L
authors.initials: SL
authors.lastname: Johansson
authors.forename: B M
authors.initials: BM
authors.lastname: McManus
mesh_terms: D001402:B-Lymphocytes; D001424:Bacterial Infections / Q000473:pathology*; D002648:Child; D002675:Child, Preschool; D003586:Cytomegalovirus Infections / Q000473:pathology; D004848:Epithelium / Q000473:pathology; D005260:Female; D006505:Hepatitis / Q000209:etiology / Q000473:pathology; D006801:Humans; D007694:Killer Cells, Natural / Q000502:physiology*; D008221:Lymphoid Tissue / Q000473:pathology*; D008589:Meningococcal Infections / Q000473:pathology; D010587:Phagocytosis; D011014:Pneumonia / Q000209:etiology / Q000473:pathology; D018805:Sepsis / Q000473:pathology; D013290:Streptococcal Infections