Growth of diploid, epstein‐barr virus‐carrying human lymphoblastoid cell lines heterotransplanted into nude mice under immunologically privileged conditions

Abstract

Human Epstein-Barr virus-carrying lymphoid cell lines which have 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 were inoculated intracerebrally into nude mice. All eighteen of them grew, killing the host mice within 7 to 25 days, except for 2 which grew more slowly. At autopsy, the brain of the nudes was found to be invaded by infiltrating lymphomas. Sixteen of these lymphomas, when recultured in vitro, gave rise to cell lines with growth properties and morphology indistinguishable from those of the inoculated LCL. Chromosomal examinations showed that 3/7 cell lines injected, which grew as lymphomas in the brain, were still normal diploid on reexplantation whereas the remaining four had become aneuploid. Four lines derived from intracerebral lymphomas (2 diploid, 1 aneuploid and 1 untested) were inoculated subcutaneously into adult nude mice. None of them grew. When the corresponding four original LCL lines were inoculated subcutaneously into newborn nude mice, they grew rapidly, but failed to do so in newborn normal mice or intracerebrally in adult normal mice. One such line, U-1450, was treated with anti-lymphocyte serum (ALS). Small nodules developed at the site of inoculation. From one nodule a cell line was cultured, 1450 ALSAD. It was morphologically indistinguishable from the line of origin. The lines obtained from nude mice inoculated with polyclonal LCL seem to have a restricted clonal representation, but were not monoclonal, as evidenced by analyses of their pattern of immunoglobulin synthesis.

Considerations in the use of nude mice for cancer research

“…In some cases, benign tissues that had been inadvertently transplanted with tumor survived, while the accompanying tumor regressed completely. Successful xenografting of transformed lymphocytes (28), and of a cell line derived from human fetal liver (29), has been reported. Both normal and pathologic tissues from a variety of sources have been shown to survive and undergo experimental manipulation, including breast (30), skin (31,32), cartilage (33), synovium (34), and others (35).…”

Differentiation-dependent sensitivity of human B-cell-derived lines to major histocompatibility complex-restricted T-cell cytotoxicity.

“…LCLs of relatively recent origin are diploid, have a low agarose clonability, and do not grow in nude mice. BL cells carry one of the three immunoglobulin locus/myc oncogene (MYC) translocations, are clonable in agarose, and grow in nude mice (9)(10)(11)(12)(13). Nearly all BLs that arise in highly endemic regions carry EBV genomes (BLE+) (14).…”

Epstein-Barr virus-transformed pro-B cells are prone to illegitimate recombination between the switch region of the mu chain gene and other chromosomes.

“…EBVcarrying BL-derived cell lines have an 8;14, 2;8, or 8;22 (IGH/MYC) translocation (22,23) and are easily cloned and highly tumorigenic. After prolonged in vitro culturing, LCLs may become aneuploid and tumorigenic (21,24). Their chromosomal anomalies are largely numerical, however, and they do not carry BL-type translocations (22,25).…”