BCL-6 Mutations in Pulmonary Lymphoproliferative Disorders:Demonstration of an Aberrant Immunological Reaction in HIV-Related Lymphoid Interstitial Pneumonia

摘要

We used a PCR and sequence procedure to analyze the Ig V_H gene and the mutations in the 5' regulatory regions of BCL-6 genes in pulmonary lymphoproliferative disorders(mucosa-associated lymphoid tissue(MALT)lymphoma,HIV-related,EBV-related,and virus-negative lymphocytic interstitial pneumonia(LIP)).Eight of 20(40%)pulmonary MALT lymphoma and 10 of 20 LIP(5 of 5(100%)HIV-related,2 of 5(40%)EBV-related,and 3 of 10(30%)virus-negative LIP)cases showed BCL-6 gene mutations.Intraclonal heterogeneity of the BCL-6 mutations was observed only in pulmonary MALT lymphoma cases whose Ig V_H genes also showed intraclonal heterogeneity.Ongoing BCL-6 mutations might reflect re-entry into a germinal center pathway to further mutations.BCL-6 mutations in pulmonary MALT lymphoma and HIV-negative LIP showed some features(high transition to transversion ratio,standard polarity,and RGYW/WRCY bias)of Ig V_H gene hypermutation,leading to the view that pulmonary MALT lymphomas and HIV-negative LIP are under the influence of germinal center hypermutation mechanisms.Because BCL-6 mutations in HIV-related LIP cases did not demonstrate features of Ig V_H gene hypermutation,immunological reactions in HIV-related LIP are the result of a process different from that found in HIV-negative pulmonary lymphoproliferative disorders.