Bone marrow stromal cells and interleukin-7 induce coordinate expression of the BP-1/6C3 antigen and pre-B cell growth.
The BP-1/6C3 molecule expressed by early B lineage cells and some stromal cells is a type II integral membrane glycoprotein that belongs to the zinc-dependent family of metallopeptidases. In order to explore the potential role of this cell surface molecule in precursor B cell proliferation, we established a stromal cell line (BHM) from long-term bone marrow cultures of the Whitlock - Witte type and developed a rapid bioassay for the detection of responsive target cells. When non-adherent bone marrow cells were cultured with BHM stroma, we observed an up-regulation of BP-1 expression by the B cell precursors that coincided with the induction of proliferation. The precursor B-cell targets included bone marrow cells that lacked detectable BP-1/6C3, B220, and Ia antigens. They could be identified in fetal liver and in the bone marrow, but not the thymus, spleen, or lymph nodes, of normal BALB/c mice, and were also present in the bone marrow of mice with the nu/nu, CBA/N, and SCID defects. Because the inductive effects on precursor B cells could be reproduced with BHM supernatant, soluble growth factors were evaluated in the assay. Interleukin 7 (IL-7) appeared to be unique in its ability to induce BP-1/6C3 expression and concomitant cell growth. Northern blot analysis revealed that the BHM stromal cells, which themselves express the BP-1 antigen, constitutively expressed high levels of variable length transcripts for IL-7. The data suggest that the IL-7 product of stromal cells selectively induces BP-1/6C3 expression on B cell precursors and may implicate this cell surface glycoprotein in the control of IL-7 induced proliferation of early B lineage cells.
Welch
P A
PA
Division of Developmental and Clinical Immunology, University of Alabama, Birmingham 35294.
Burrows
P D
PD
Namen
A
A
Gillis
S
S
Cooper
M D
MD
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000201:enzymology / Q000276:immunology*; D001854:Bone Marrow Cells; D002455:Cell Division; D002460:Cell Line; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000201:enzymology / Q000276:immunology; D015851:Interleukin-7 / Q000235:genetics / Q000276:immunology / Q000494:pharmacology*; D008666:Metalloendopeptidases / Q000096:biosynthesis* / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology
D015851:Interleukin-7; D012333:RNA, Messenger; C062906:BP-1-6C3 antigen; D008666:Metalloendopeptidases