We have previously demonstrated that IL-7 can sustain the growth of no
rmal human B cell precursors (BCP) for several weeks on bone marrow-de
rived stromal cells. Flow cytometric analysis of BCP recovered from IL
-7 supplemented cultures revealed two- to threefold higher levels of c
ell surface CD19, compared with BCP maintained without IL-7. Short ter
m culture of BCP showed that IL-7 enhancement of CD19 was dose-depende
nt, with increases detected by day 1 and plateauing by days 3 to 4. IL
-7 increased cell-surface CD1 9 on small lymphoid cells, and to a grea
ter degree on lymphoblasts, whereas cell-surface CD10 was unchanged. T
he CD34+/CD19+ pro-B cell population showed a greater increase in cell
-surface CD19 compared with pre-B and immature B cells. IL-1, IL-3, IL
-4, IL-6, and stem-cell factor had no effect on CD19. The potential fu
nctional significance of IL-7-enhanced cell-surface CD19 was examined
using a F(ab')2 fragment of anti-CD19. This reagent had no effect on [
H-3]TdR incorporation in BCP cultured in the absence or presence of IL
-7 for 5 days, but homotypic adhesion of BCP was induced at a concentr
ation as low as 1.0 ng/ml F(ab')2 anti-CD19. IL-7 enhanced the F(ab')2
anti-CD19 induced homotypic adhesion of BCP in a dose-dependent manne
r. Blocking antibody studies indicated that members of the beta1 or be
ta2 integrin families did not mediate anti-CD19-induced homotypic adhe
sion, even though the adhesion was completely ablated by 10 mM EDTA. T
he pre-B and immature leukemic B cell lines NALM-6 and 1E8 expressed c
omparable levels of cell-surface CD19, and exhibited comparable increa
ses after IL-7 stimulation. However, their homotypic adhesion response
s to anti-CD19 were different. NALM-6 cells exhibited a strong homotyp
ic adhesion response to anti-CD19 that was EDTA-resistant, and beta1/b
eta2 integrin independent. 1E8 cells only responded to anti-CD19 after
IL-7 stimulation; this response was EDTA-sensitive and beta1/beta2 in
tegrin independent. These collective results indicate that IL-7 not on
ly acts as a growth factor for human BCP, but also regulates signal tr
ansduction through cell-surface CD19.