The Journal of Immunology, Vol 151, Issue 1 138-148, Copyright © 1993 by American Association of Immunologists

ARTICLES

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

ML Wolf, WK Weng, KT Stieglbauer, N Shah and TW LeBien
Department of Laboratory Medicine and Pathology, University of Minnesota Medical School, Minneapolis 55455.

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 beta 1 or beta 2 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 beta 1/beta 2 integrin independent. 1E8 cells only responded to anti-CD19 after IL-7 stimulation; this response was EDTA- sensitive and beta 1/beta 2 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.

This article has been cited by other articles:

				N. Shah, L. Oseth, H. Tran, B. Hirsch, and T. W. LeBien Clonal Variation in the B-Lineage Acute Lymphoblastic Leukemia Response to Multiple Cytokines and Bone Marrow Stromal Cells Cancer Res., July 1, 2001; 61(13): 5268 - 5274. [Abstract] [Full Text] [PDF]

				T. W. LeBien Fates of human B-cell precursors Blood, July 1, 2000; 96(1): 9 - 23. [Abstract] [Full Text] [PDF]

				M. E. Donohoe, G. B. Beck-Engeser, N. Lonberg, H. Karasuyama, R. L. Riley, H.-M. Jack, and B. B. Blomberg Transgenic Human {lambda}5 Rescues the Murine {lambda}5 Nullizygous Phenotype J. Immunol., May 15, 2000; 164(10): 5269 - 5276. [Abstract] [Full Text] [PDF]

				F.E. Bertrand III, L.G. Billips, P.D. Burrows, G.L. Gartland, H. Kubagawa, and H.W. Schroeder Jr Ig DH Gene Segment Transcription and Rearrangement Before Surface Expression of the Pan-B-Cell Marker CD19 in Normal Human Bone Marrow Blood, July 15, 1997; 90(2): 736 - 744. [Abstract] [Full Text] [PDF]

				D. H. Ryan, B. L. Nuccie, I. Ritterman, J. L. Liesveld, C. N. Abboud, and R. A. Insel Expression of Interleukin-7 Receptor by Lineage-Negative Human Bone Marrow Progenitors With Enhanced Lymphoid Proliferative Potential and B-Lineage Differentiation Capacity Blood, February 1, 1997; 89(3): 929 - 940. [Abstract] [Full Text] [PDF]