The immunological architecture of B-lymphocyte aggregates in cryptogenic fibrosing alveolitis.

Cryptogenic fibrosing alveolitis (CFA) is believed to have a pathogenesis mediated by the cellular arm of the immune system. Previous studies have, however, indicated the presence of B-lymphocyte aggregates, as well as evidence of local immunoglobulin production and increased levels of B-cell growth factors. It has recently been shown that CFA is associated with the production of circulating IgG autoantibodies to antigen(s) associated with alveolar lining cells. This prompted an examination of the immunological architecture of the B-lymphocyte aggregates, in order to assess whether they might provide histological confirmation of a local humoral immune response in these patients. Thirty-eight consecutive open lung biopsy specimens were examined from patients with CFA and aggregates of B lymphocytes were identified in 37/38. In only five cases were germinal centres seen. The morphological appearances of the aggregates were reminiscent of those observed in mucosal associated lymphoid tissue (MALT). Using immunohistochemistry, despite the low frequency of true germinal centre formation, the B-lymphocyte aggregates were shown to contain the cellular micro-environment necessary for a humoral immune response. In addition, there was evidence of lymphocyte proliferation and activation within these aggregates. These results provide evidence of a local humoral immune response associated with B-lymphocyte aggregates in the lungs of patients with CFA.