Bone marrow stromal cells and interleukin-7 induce coordinate expression of the BP-1/6C3 antigen and pre-B cell growth

Abstract

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.