EBV Transformation Research Articles

Tumorigenicity of human hematopoietic cell lines in athymic nude mice.

Human hematopoietic cell lines, which had been classified on the basis of studies on clonality, and morphological, chromosomal and functional parameters as lymphoblastoid cell lines (LCL) of presumed non-neoplastic origin, and lymphoma, myeloma and leukemia lines of proven malignant origin, were tested for tumorigenic potential on subcutaneous transplantation to nude mice and for capacity to grow in semi-solid medium in vitro. Recently established LCL failed to grow both in nude mice and in agarose. In contrast, some of the LCL which had developed secondary chromosomal alterations during continuous cultivation for periods exceeding several years were tumorigenic and/or had the capacity to form colonies in agarose. Most lymphoma lines formed colonies in agarose and tumors in the mice. One of the two myeloma lines formed subcutaneous tumor which, however, showed no progressive growth. The other myeloma line failed to grow. Both myeloma lines, however, formed colonies in agarose. The myeloid leukemia line was tumorigenic while two of the three tested lymphocytic leukemia lines failed to grow in the mice. All leukemia lines formed colonies in agarose. We conclude from this study that: (1) Of the two types of Epstein-Barr virus containing cell lines [LCL and Burkitt lymphoma (BL) lines], only BL lines were shown to form tumors when inoculated subcutaneously in nude mice and had the capacity to grow in agarose in vitro. This shows that EBV transformation per se does not necessarily render lymphocytes tumorigenic in nude mice. The capacity to form colonies in agarose is not acquired either. (2) Changes of the karyotype and several phenotypic characteristics which occur in the originally diploid LCL during prolonged cultivation in vitro may be accompanied by the acquisition of the potential to grow subcutaneously in nude mice and in agarose in vitro. (3) The inconsistency with regard to the capacity of come of the neoplastic cell lines to grow in nude mice or in agarose seems to underline that neither of the two tests is a reliable criterion for malignancy of human lymphoma, leukemia and myeloma cell lines.

ACQUIRED AGAMMAGLOBULINEMIA IN 3 RELATED MALE CHILDREN FOLLOWING AN ILLNESS WITH CLINICAL AND LABORATORY FEATURES OF INFECTIOUS MONONUCLEOSIS

Three male children in 1 family (2 siblings and 1 maternal cousin) have presented with an illness characterized by cervical adenopathy, hepatosplenomegaly, fever and subsequent development of agammaglobulinemia in the 2 survivors. Both siblings presented at age 8 with positive heterophile titers. EBV titers were not obtained. The maternal cousin became ill at age 6 months; EBV antibodies were detected on 3 occasions but the heterophile titer was negative. Peripheral WBC rose to a level of 120,000/mm3 with 90% lymphocytes, most being “atypical” in morphology. Evaluation of peripheral blood lymphocytes at the height of the illness showed 94% T-cells and 6% B-cells with normal lymphocyte transformation in response to phytohemagglutinin. Immunoglobulin analysis initially showed marked IgM elevation with normal IgA and decreased IgG. Subsequently serial analyses revealed absence of the 3 major immunoglobulins. Lymph node biopsies of the surviving sibling and cousin showed replacement of normal architecture by necrotic material. The association (x-linked) of acquired agammaglobulinemia following an illness with features of infectious mononucleosis has not been previously reported. Its pathogenesis may involve an abnormal T-cell response to EBV transformation of B-cells leading to B-cell dysfunction, lymph node necrosis, and agammaglobulinemia.