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 Blood, 15 December 2004, Vol. 104, No. 13, pp. 4252-4259.
Prepublished online as a Blood First Edition Paper on August 26, 2004; DOI 10.1182/blood-2004-04-1245.

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NEOPLASIA

Mycoplasma fermentans infection promotes immortalization of human peripheral blood mononuclear cells in culture

Shimin Zhang, Shien Tsai, Timothy T. Wu, Bingjie Li, James W.-K. Shih, and Shyh-Ching Lo

From the Department of Infectious and Parasitic Diseases Pathology, American Registry of Pathology, Washington, DC; Department of Transfusion Medicine, Warren Grant Magnuson Clinical Center, National Institutes of Health, Bethesda, MD; and Department of Infectious and Parasitic Diseases Pathology, Armed Forces Institute of Pathology, Washington, DC.

Chronic infection or colonization by mycoplasma(s) could gradually and significantly alter many biologic properties of mammalian host cells in culture, including induction of malignant transformation. We examined effects of Mycoplasma fermentans infection on the continuing survival and immortality of human peripheral blood mononuclear cells (PBMCs) from healthy blood donors. Without specific supplemental growth factors, human PBMCs normally die rapidly, with few cells other than macrophages/monocytes surviving after 2 weeks in cultures. Only occasional Epstein-Barr virus (EBV)–positive B lymphocytes would continue to proliferate and undergo spontaneous immortalization. Our present study revealed that infection of human PBMCs in culture with the incognitus and PG18 strains of M fermentans, but surprisingly not with some other strains tested in parallel, markedly enhanced the rate of EBV-positive B lymphocytes to undergo immortalization (74% vs 17%). Compared with spontaneously immortalized PBMCs, the PBMCs immortalized in cultures infected with the mycoplasmas often had prominent karyotype changes with chromosomal loss, gain, or translocations. Furthermore, many of these immortalized B lymphocytes were found to be monoclonal in nature. The in vitro findings would be of relevance to lymphoproliferative disorders that occurred in patients with immune suppression. The mycoplasma-mediated promotional effect in cell immortalization and its potential clinical implications warrant further study.


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