B lymphocyte accumulations in human pulmonary sarcoidosis.
Fazel SB., Howie SE., Krajewski AS., Lamb D.
BACKGROUND: Although cell mediated immunity is primarily thought to mediate the pathogenesis of sarcoidosis, the presence of immunoglobulins, immune complexes and complement suggests that processes of humoral immunity may contribute to immunopathology in sarcoid lesions. To test this hypothesis, the distribution of B lymphocytes in paraffin embedded sarcoid lesions in mediastinal lymph nodes and open lung biopsy specimens was investigated. METHODS: Paraffin sections from eight open lung and 21 lymph node biopsies from sarcoid patients and five normal and five tuberculous lymph nodes from patients with tuberculosis were stained with a panel of monoclonal antibodies by means of avidin/biotin enhanced immunocytochemistry. RESULTS: Immunohistochemical analysis of the 29 biopsy specimens from the sarcoid patients revealed large numbers of B cells in the intergranulomatous regions. Further investigations in the open lung biopsy specimens indicated that these B cells were often organised into discrete circular or oval shaped aggregates with no germinal centre morphology, in which a few CD45RO memory T lymphocytes were scattered. The B cells were polyclonal, and a few plasma cells (IgM+, IgA+, IgG+) were identified. CONCLUSIONS: The finding of large numbers of B lymphocytes in sarcoid pulmonary lesions is in contrast to bronchoalveolar lavage studies, which have demonstrated proportions of 5% or less of B cells as a total of all immune cells, and therefore indicates that bronchoalveolar lavage may not correctly sample the immune cells of lung interstitial tissue in pulmonary sarcoidosis. The B cells at these sites are the possible origin of some of the humoral changes in the serum and lesions of sarcoid patients. They may also influence the pathogenesis of the disorder by presenting antigen(s) and forming immune complexes at sites of disease activity.