Functional effect of IL-7-enhanced CD19 expression on human B cell precursors

M. L. Wolf, W. K. Weng, K. T. Stieglbauer, N. Shah, T. W. LeBien

Research output: Contribution to journalArticlepeer-review

30 Scopus citations

Abstract

We have previously demonstrated that IL-7 can sustain the growth of normal human B cell precursors (BCP) for several weeks on bone marrow-derived stromal cells. Flow cytometric analysis of BCP recovered from IL-7 supplemented cultures revealed two- to threefold higher levels of cell surface CD19, compared with BCP maintained without IL-7. Short term culture of BCP showed that IL-7 enhancement of CD19 was dose-dependent, with increases detected by day 1 and plateauing by days 3 to 4. IL-7 increased cell-surface CD19 on small lymphoid cells, and to a greater degree on lymphoblasts, whereas cell-surface CD10 was unchanged. The 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 functional 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 [3H]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 concentration 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 manner. Blocking antibody studies indicated that members of the β1 or β2 integrin families did not mediate anti-CD19-induced homotypic adhesion, even though the adhesion was completely ablated by 10 mM EDTA. The pre-B and immature leukemic B cell lines NALM-6 and 1E8 expressed comparable levels of cell-surface CD19, and exhibited comparable increases after IL-7 stimulation. However, their homotypic adhesion responses to anti-CD19 were different. NALM-6 cells exhibited a strong homotypic adhesion response to anti-CD19 that was EDTA-resistant, and β1/β2 integrin independent. 1E8 cells only responded to anti-CD19 after IL-7 stimulation; this response was EDTA-sensitive and β1/β2 integrin independent. These collective results indicate that IL-7 not only acts as a growth factor for human BCP, but also regulates signal transduction through cell-surface CD19.

Original languageEnglish (US)
Pages (from-to)138-148
Number of pages11
JournalJournal of Immunology
Volume151
Issue number1
StatePublished - 1993

Fingerprint

Dive into the research topics of 'Functional effect of IL-7-enhanced CD19 expression on human B cell precursors'. Together they form a unique fingerprint.

Cite this