The Journal of Immunology, 2004, 172: 7116-7122.
Copyright © 2004 by The American Association of Immunologists
BCL-6 Mutations in Pulmonary Lymphoproliferative Disorders: Demonstration of an Aberrant Immunological Reaction in HIV-Related Lymphoid Interstitial Pneumonia1
Katsushi Kurosu2,*,
Michael D. Weiden
,
Yuichi Takiguchi*,
William N. Rom
,
Norio Yumoto
,
Jagirdar Jaishree
,
Koh Nakata
,
Yasunori Kasahara*,
Nobuhiro Tanabe*,
Koichiro Tatsumi*,
Atsuo Mikata
and
Takayuki Kuriyama*
* Department of Respirology (B2) and
Department of Pathology, School of Medicine, Chiba University, Chiba, Japan;
Division of Pulmonary and Critical Care Medicine and Bellevue Chest Service and
Department of Pathology, New York University Medical Center, New York, NY 10016
We used a PCR and sequence procedure to analyze the Ig VH 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 VH 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 VH 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 VH gene hypermutation, immunological reactions in HIV-related LIP are the result of a process different from that found in HIV-negative pulmonary lymphoproliferative disorders.
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