Abstract
Five stromal-cell-dependent lymphocyte clones are described that correspond to late pre-B
or early B-cell stages of differentiation.They are useful for determining the molecular
requirements for pre-B replication, for studying the stromal cells that supply those factors,
and for delineating the final sequence of differentiation events as newly formed lymphocytes
prepare to exit the bone marrow. The efficiency of lymphocyte growth at limiting dilution
varied substantially on different stromal-cell clones and may reflect functional heterogeneity
of stromal cells. Most lymphocyte clones were similar to uncloned lymphocytes from
Whitlock-Witte cultures in that they responded only transiently to interleukin-7 (IL-7) and
then died, unless maintained on a stromal-cell clone. One unusual lymphocyte clone (2E8)
was propagated for more than 1 year in IL-7 alone and was selectively responsive to that
cytokine. Most of the lymphocyte clones were not tumorigenic in immunodeficient mice.
However, one pre-B clone (1A9)’grew autonomously in culture when held at high density,
responded to conditioned medium from a number of cell lines, and was tumorigenic.
Tumors derived from this clone were infiltrated by stromal cells and lymphocytes taken
from the tumors' retained characteristics of the original clone. Ly-6 antigens were inducible
on 2E8 and 1A9 cells, but the lymphocytes were otherwise arrested in differentiation. The
2E8 cells had rearranged and expressed