B-lymphocytes in tissues such as spleen and lymph nodes could be an in vivo reservoir for XMRV

Development of XMRV producing B Cell lines from lymphomas from patients with Chronic Fatigue Syndrome

Francis Ruscetti1 , Vincent C Lombardi2, Michael Snyderman3, Dan Bertolette4, Kathryn S Jones1 and Judy A Mikovits1:

1 Center for Cancer Research NCI-Frederick, Frederick, Maryland, 21702, USA
2 Whittemore Peterson Institute, University of Nevada, Reno, Nevada, 89557, USA
3 Department of Medicine, State University of New York at Buffalo, Buffalo, New York, USA
4 Basic Research Program, SAIC-Frederick, Inc., NCI-Frederick, Frederick, Maryland, 21702, USA
author email corresponding author email

from 15th International Conference on Human Retroviruses: HTLV and Related Viruses
Leuven and Gembloux, Belgium. 5-8 June 2011

Retrovirology 2011, 8(Suppl 1):A230doi:10.1186/1742-4690-8-S1-A230

The electronic version of this abstract is the complete one and can be found online at: http://www.retrovirology.com/content/8/S1/A230

Published: 6 June 2011
© 2011 Ruscetti et al; licensee BioMed Central Ltd.


Meeting abstract

Previous studies have shown that CFS patients have an increased incidence of lympho-proliferative malignancy compared to the normal population [1]. While the incidence rate of non-Hodgkin’s lymphoma in the United States is 0.02%, nearly 5% of the CFS patients developed the disease. Additionally, development of cancer coincides with an outgrowth of gamma delta T cells with specific clonal T-cell receptor gamma rearrangements. We hypothesized that infection with XMRV and/or other viruses can trigger a dysregulated immune response which favors the development of B-cell lymphoma.

In a study of 300 CFS patients, 13 developed lymphoproliferative disorders. Of those tested, 11/11 were positive for XMRV and 9/9 positive for clonal TCR gamma rearrangements. Spontaneous development of four B cells lines occurred during culture of cells from CFS patients. Three developed from B cells isolated from the peripheral blood (two of whom had B cell lymphoma) and one from a bone marrow biopsy. For all four lines, the B cells have a mature CD20+, CD23+ phenotype and produce infectious XMRV at a titer of >106 infectious units/ml. Virus production occurred despite extensive hypermutation of the proviruses in these cells by APOBEC3G.. Therefore XMRV infection may accelerate the development of B cell malignancies by either indirect chronic stimulation of the immune system and/or by direct infection of the B-cell lineage . Since viral load in peripheral blood is low, these data suggest that B cells in tissues such as spleen and lymph nodes could be an in vivo reservoir for XMRV.

B-lymphocytes play a significant role in the ongoing clinical features of ME/CFS