Oligoclonal expansion of B cells in the livers of hepatitis C virus infection may be associated with the development of B-cell non-Hodgkin lymphomas.

J Murakami,MD,PhD, Y Shimizu,MD,PhD, Y Kashii, MD,PhD, K Ebata, MD, T Kato, MD,A Watanabe, MD, PhD

Toyama Medical and Pharmaceutical University, Toyama, Toyama Japan

AIM: The prevalence of HCV infection in patients with B-cell non-Hodgkin's lymphomas is higher than that in general populations. To investigate the molecular mechanism for the association between hepatitis C virus (HCV) infection and B-cell lymphomas, we analyzed the B-cell response in the liver of HCV infection by immunohistochemistry and polymerase chain reaction (PCR). METHODS: Eighteen liver specimens of chronic hepatitis C and four of normal livers were used. For immunohistochemical study, immunoglobulin (Ig)M, IgD, IgG, CD10, CD20, (B cell markers) Ki-67 (proliferation marker), bcl-2 (anti-apoptotic molecule), bcl-6 (marker for germinal center formation), CD23 (marker for dendritic cells, macrophages and B cells) and CD81 (putative HCV receptor) were stained by using specific antibodies. Ig heavy chain (IgH) gene rearrangement in the liver was examined to analyze the clonality of B cells by PCR. RESULTS: Germinal center (GC) formation in the intrahepatic lymphoid follicles (LIFs) was frequently found in HCV-positive cases. The distribution of IgM-, IgD-, and IgG-positive cells and the expression patterns of CD10, CD20, Ki-67, CD23, bcl-2 and bcl-6 gene products in the follicles with GC formation were similar to those of lymph nodes. Moreover, CD81 was stained in GC of LIFs. PCR analysis for IgH gene rearrangement showed oligoclonal expansion of B cells in the livers with LIFs. CONCLUSIONS: Functional and oligoclonal expansion of B cells found in the livers of chronic hepatitis C, which could be induced by the persistent stimulation with HCV in GC as suggested by the expression of CD81, may be associated with the high prevalence of HCV infection in patients with B-cell non-Hodgkin lymphomas.

KEY WORDS: hepatitis C virus, B-cell, immunoglobulin heavy chain rearrangement, .

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Paper presented at the International Symposium on Predictive Oncology and Intervention Strategies; Paris, France; February 9 - 12, 2002; in the section on Predictive Markers.