In vivo localization and growth of the 70Z/3 pre-B-cell line

The 70Z/3 pre-B-cell line has long been used as a model for understanding the nature and mode of action of differentiation-inducing stimuli as well as mechanisms which control immunoglobulin light chain gene expression. This study is a first appraisal of the localization, growth, and differentiation of the cell line in vivo. At 24 hr after intravenous injection, radiolabeled 70Z/3 cells localized efficiently to the bone marrow and analysis by flow cytometry revealed that fluorescein isothiocyanate-labeled cells localized to bone marrow and spleen in a ratio of 2:1. Growth of the cell line paralleled the localization pattern. When the cells were given intravenously, bone marrow contained 100% of tumor cells at a time when a majority of spleen cells were still normal. Tumor cells were found in the blood only at end-stage disease in a minority of animals. Because 70Z/3 cells differentiate in vitro in response to a variety of factors, it is possible that exposure to the in vivo environment would have a similar effect. When blast cells from heavily infiltrated bone marrow and spleen were analyzed for the expression of a panel of B-lymphocyte lineage surface antigens, however, there was no evidence for surface kappa induction. Inductive stimuli may be present in limiting quantities in vivo or overridden by by negative feed-back control mechanisms. This information provides a basis for in vivo experimentation with the inducible 70Z/3 cell line and raises issues concerning normal mechanisms which control B-lineage cell differentiation.