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Insulin-like growth factor-I regulates pro-B cell differentiation
KS Landreth, R Narayanan and K Dorshkind
Mary Babb Randolph Cancer Center, West Virginia University School of
Medicine, Morgantown 26506.
Progression of B-lymphocyte development in the bone marrow of postnatal
mammals is marked by progressive rearrangement and expression of
immunoglobulin (Ig) heavy- and light-chain genes. Following productive
VHDJH gene rearrangement in the Ig heavy-chain gene complex, mu-heavy chain
is the first Ig gene product expressed in cells committed to the B-lymphoid
differentiation pathway. Interleukin (IL)-7 has been shown to stimulate
proliferation of pre-B cells following c mu expression and this
proliferative stimulus is potentiated by kit ligand (KL). However, it
appears that neither of these cytokines contributes to differentiation of
pro-B cells or initiation of expression of Ig gene products. We previously
demonstrated that differentiation of pro-B cells and expression of mu-heavy
chain is stimulated by either bone marrow stromal cell line S17 or
cell-free supernatants from that line. This biological activity was
attributed to molecules with an apparent M(r) of less than 10 Kd and
approximately 40 to 60 Kd. We now report that this biological activity
resides with stromal cell-derived insulin- like growth factor-I (IGF-I).
Recombinant IGF-I stimulated the expression of cytoplasmic mu-heavy chain
in short-term bone marrow cultures and this stimulus was abrogated in the
presence of anti-IGF-I antibody. We also demonstrate that either anti-IGF-I
antibody or pretreatment of S17 cells with antisense oligonucleotide for
IGF-I abrogated the pro-B cell differentiation activity of S17 stromal cell
supernatants. Although IGF-I did not directly stimulate proliferation of
B-lineage cells, like KL, it potentiated the proliferative stimulus
provided by IL-7. Taken together, these data strongly suggest that IGF- I
produced by bone marrow stromal cells in the hematopoietic microenvironment
plays a key role in regulating primary B lymphopoiesis.
Volume 80,
Issue 5,
pp. 1207-1212,
09/01/1992
Copyright © 1992 by The American Society of Hematology
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