Epstein-Barr virus-transformed human precursor B cell lines: altered growth phenotype of lines with germ-line or rearranged but nonexpressed heavy chain genes

Abstract

A series of lymphoblastoid cell lines (LCLs) have been established by in vitro infection of fetal bone marrow and fetal liver cells with Epstein-Barr virus (EBV). While most lines showed the usual mature B cell phenotype, a small proportion were cytoplasmic and surface immunoglobulin (Ig) heavy and light chain negative. Analysis of gene rearrangements indicated that the Ig- lines were either germ-line or nonproductively rearranged when probed for JH and were in germ-line configuration for C chi; no mu or chi mRNA could be detected in such cells. Precursor B cell lines were indistinguishable from their normal Ig+ counterparts in their expression of a wide variety of cell surface markers including "activation" antigens usually associated with the lymphoblastoid state; even the single LCL showing germ-line heavy and light chain genes expressed B lineage-specific cell surface antigens. However, the Ig- lines were distinct from their Ig+ counterparts in three important respects: (a) they grew much more slowly and achieved lower saturation densities, (b) they showed unusually high proportions (8-16%) of cells in EBV-productive cycle, and (c) they contained unusually high proportions (up to 40%) of cells expressing free joining (J) chain. These results suggest that precursor B cells differ in their response to the growth-transforming effects of EBV such that the virus-cell interaction in precursor B cell lines is inherently less stable than in conventional LCL. In particular there may be a greater movement of cells out of cycle and along the B cell maturation pathway. It is possible that such movement leads in individual cells either to virus replication or to a "sterile" plasmacytoid differentiation with J chain expression in the absence of Ig synthesis.