Heterotransplantation of Two Human Lymphoid Cell Lines Transformed In Vitro by Epstein-Barr Virus

Abstract

The in vivo biologic activity of 2 human lymphoid cell lines (AV₁ and JQ), established after in vitro transformation by Epstein-Barr virus (EBV), was studied. (BALB/c × A/HeN)F₁ mice, in the first 24 hours of life, were pretreated with rabbit antilymphocyte serum and then given intraperitoneal injections of varying doses of living cells. Of 30 mice that received 1 × 10⁷-10⁸ AV¹ cells, 28 developed tumors and died; but, of 40 mice given lower doses, none died. JQ cells caused fatal tumors at a dose as low as 5 × 10⁶. There was gross tumor involvement of all intra-abdominal organs, retroperitoneal structures, and surrounding muscular areas. Microscopically, all organs except the heart were invaded by very aggressive, undifferentiated lymphoid cells. Negative controls consisted of buffy-coat lymphocytes from 2 donors without serologic evidence of previous EBV infection. One of these seronegative donors contributed the cells from which the in vitro EBV-transformed cell line AV¹ was established. We conclude that EBV can cause human lymphocytes to grow in an uncontrolled and highly invasive manner in a heterologous host. Possibly the EBV genome is necessary for the heterotransplantability of most, but possibly not all, continuous human lymphoid cell lines.