LFA-1-Mediated Adhesion Of Human Hematopoietic Progenitors To Bone Marrow Stromal Cells Enhances B-Lineage Differentiation Toward CD19+ ProB Cells, While The Generation Of CD7+CD56-CD45RA+ Multipotent Lymphoid and CD10+CD19- B-Biased Progenitors Is Supported By Soluble Factors Produced From Stromal Cells

The regulatory mechanism of human lymphoid differentiation remains less defined. Here we examined how bone marrow stromal cells regulate human early lymphoid differentiation, using human telomerized bone marrow stromal cells that support the generation of CD7+CD56- early T and CD10+CD19+ proB cells from human hematopoietic progenitors. To examine the role of direct contact between hematopoietic progenitors and stromal cells in lymphopoiesis, cultures were performed by inhibiting the cell-cell contact with microporous insert or by incubating hematopoietic progenitors with conditioned medium collected from stromal cell cultures. The separation suppressed B-lineage differentiation to CD10+CD19+ cells, while the generation of CD7+ cells was not significantly influenced. The CD7+ cells generated with or without direct contact with stromal cells similarly had multipotent differentiation capacity for T, B, NK, granulocytic, and monocytic cells but not for erythroid cells in various culture conditions. On the other hand, even CD10+CD19- immature cells had more limited differentiation capacity for T, B, and monocytic cells in various culture conditions, and mostly differentiated toward CD10+CD19+ proB cells on the stromal cells. By time course analysis after coculture on the stromal cells, CD7+CD10- followed by CD10+CD19- and then CD10+CD19+ cells were developed. Some portion of CD7+CD10- and most of CD7-CD10+CD19- cells, upon recultured on stromal cells, differentiated toward CD10+CD19+ cells, but such B-lineage differentiation on the stromal cells was diminished by reculture with conditioned medium. ICAM-1 was expressed on the telomerized stromal cells. Coculture on stromal cells in the presence of LFA-1 neutralizing antibody that blocks the binding to ICAM-1 inhibited the differentiation to CD19+ proB cells. Our findings show that stromal cells support the generation of CD7+ multipotent lymphoid and CD10+ B-biased progenitors by producing soluble factors, but enhances B-lineage differentiation toward CD19+ proB cells in part via LFA-1-mediated direct cell-cell contact.