The latency-associated nuclear antigen of Kaposi sarcoma–associated herpesvirus induces B cell hyperplasia and lymphoma
Farnaz D. Fakhari, Joseph H. Jeong, Yogita Kanan, Dirk P. Dittmer
Farnaz D. Fakhari, Joseph H. Jeong, Yogita Kanan, Dirk P. Dittmer
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Research Article Immunology

The latency-associated nuclear antigen of Kaposi sarcoma–associated herpesvirus induces B cell hyperplasia and lymphoma

Abstract

Kaposi sarcoma–associated herpesvirus (KSHV) is a human lymphotropic herpesvirus. It is implicated in B cell neoplasias such as primary effusion lymphoma and multicentric Castleman disease in AIDS patients. The KSHV latency-associated nuclear antigen (LANA) is consistently expressed in all KSHV-associated tumor cells and was shown to bind the tumor suppressor proteins p53 and pRb. To test LANA’s contribution to lymphomagenesis in vivo we generated transgenic mice expressing LANA under the control of its own promoter, which is B cell specific. All of the transgenic mice developed splenic follicular hyperplasia due to an expansion of IgM+IgD+ B cells and showed increased germinal center formation. We also observed lymphomas, implying that LANA can activate B cells and provide the first step toward lymphomagenesis.

Authors

Farnaz D. Fakhari, Joseph H. Jeong, Yogita Kanan, Dirk P. Dittmer

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Figure 7

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PCR analysis of VDJH and DJH rearrangements in tumors of LANA transgenic...
PCR analysis of VDJH and DJH rearrangements in tumors of LANA transgenic mice. Total spleen genomic DNAs were used in the PCR reactions analyzing tumors. (A–C) PCR analysis of total spleen genomic DNAs from 4 LANA transgenic mice with tumors, 2 C57BL/6 mice older than 300 days (WT), and 2 different murine B cell lines resolved on a 1.5% Tris-acetate-EDTA–agarose gel, used as controls for the clonality. WT lanes demonstrate VDJH1, VDJH2, VDJH3, and VDJH4 rearrangements (A and B) using VH7183 (A) or VHJ558 primers (B) and DJH1, DJH2, DJH3, and DJH4 rearrangements (C) using Dq52 primers. The primers were designed to amplify all rearrangement products between JH4 and VH7183, VHJ558, or Dq52; 4 different bands would be expected by the combination of each primer set. M, 100-bp DNA Ladder (New England Biolabs Inc.) (D) DNA samples used for the Ig rearrangement PCRs were quantified using real-time quantitative PCR to demonstrate equal total DNA concentrations.