Direct Contact with Stromal Cells in Association with SDF-1 Is Important for B-Lineage Differentiation Toward CD19⁺ ProB Cells from Human Hematopoietic Precursors, but Dispensable for Generation of CD7⁺CD45RA⁺ Multipotent Lymphoid Precursors

The regulatory mechanism of human early B- and T- lymphoid differentiation has not been well studied. Coculture on telomerized human bone marrow stromal cells supported the generation of CD7⁺CD45RA⁺ multipotent precursors with differentiation potential for T-, B-, NK-lineage, and monocytic cells, CD10⁺CD19^-CD45RA⁺ B-biased precursors, and CD10⁺CD19⁺CD45RA⁺ proB cells from human CD34⁺lin^- hematopoietic progenitors. CD7⁺CD45RA⁺ and CD10⁺CD19^- lymphoid precursors can be developed from hematopoietic progenitors by soluble factors produced from stromal cells, but the generation of CD19⁺ proB cells was reduced. Replating analysis showed that direct contact with stromal cells promoted B-lineage differentiation toward CD19⁺ proB cells from CD34⁺lin^- cell-derived CD7⁺CD45RA⁺ and CD10⁺CD19^- lymphoid precursors.

SDF-1 is shown to be critical for B-lineage differentiation from studies of mice. SDF-1 was produced from the human telomerized stromal cells. Inhibition of binding to SDF-1 with neutralizing antibody against CXCR4 suppressed B-lineage differentiation to CD19⁺ proB cells from hematopoietic precursors, while the generation of CD7⁺CD45RA⁺ cells was not significantly affected. By replating analysis, anti-CXCR4 Ab inhibited the differentiation to CD19⁺ proB cells from CD7⁺CD45RA⁺ and CD10⁺CD19^- lymphoid precursors on stromal cells.

These data indicate that direct contact with stromal cells in association with SDF-1 produced from stromal cells is important for B-lineage differentiation toward CD19⁺ proB cells from CD7⁺CD45RA⁺ and CD10⁺CD19^- lymphoid precursors but dispensable for differentiation toward CD7⁺CD45RA⁺ multipotent lymphoid precursors.