B-cell precursors differentiated from cord blood CD34+ cells are more immature than those derived from granulocyte colony-stimulating factor-mobilized peripheral blood CD34+ cells

摘要

Umbilical cord blood (CB) has been widely used instead of bone marrow (BM) and peripheral blood (PB) for stem cell transplantation (SCT). However, problems of sustained immunodeficiency after CB transplantation remain to be resolved. To elucidate the mechanism of immunodeficiency, we compared the characteristics of B cells differentiated in vitro from CD34+ cells of CB with those of PB. Purified CD34+ cells from CB and PB were cultured on murine stroma cell-line MS-5 with stem cell factor and granulocyte colony-stimulating factor for 6 weeks. The B-cell precursors (pre-B cells) that differentiated in this culture system, were analysed as to their immunoglobulin heavy chain (IgH) variable region gene repertoire and the expression of B-cell differentiation-related genes. CD10+ CD19+ pre-B cells were differentiated from both PB and CB. Although the usages of IgH gene segments in pre-B cells differentiated from CB and PB were similar, the N region was significantly shorter in CB-derived than PB-derived cells. Productive rearrangements were significantly fewer in cells of CB than PB in the third week. Among a number of B-cell differentiation-related genes, the terminal deoxynucleotidyl transferase (TdT) gene was not expressed in CB-derived cells during the culture. These results indicated that immature features of pre-B cells from CB, such as lack of TdT expression, and a short N region and few productive rearrangements in the IgH gene, might cause the delay in mature B-cell production.