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. Disclosures No relevant conflicts of interest to declare.