CD27 expression patterns on human developing B cells in fetal and adult tissues (111.27)

Abstract

Abstract CD27 is an accepted marker for memory B cells in humans. However, CD27 expression was recently demonstrated on substantial populations of human B cells in cord blood and fetal liver (FL), tissues that contain few if any memory B lymphocytes. In addition, CD27 expression was recently proposed to identify natural B cells, the human counterpart of murine B-1 B cells. These observations led us to explore the characteristics of human, CD27+ B cells, and particularly developing B cells. Comparing B cells from FL, cord blood, and adult bone marrow (BM), we found CD27 expression as early as the pro-B cell stage. Moreover, the frequency of CD27+ pro-B cells was higher in FL than in BM. Expression of TdT, RAG1 and VpreB in CD27+ pro-B cells was similar to conventional, CD27- pro-B cells, confirming their identity as B-lineage progenitors. Developmentally immature CD27- and CD27+ B cells showed no significant differences in VH gene usage, VH mutation frequencies, or CDRH3 length, excluding the possibility of contamination by memory B cells. Interestingly, when placed in an in vitro culture system optimized to support the maturation of human fetal pro-B cells and murine B-1 B cells, CD27+ pro-B cells differentiated into IgM+ immature and transitional B cells significantly more efficiently than did autochthonous CD27- pro-B cells. In conclusion, we have demonstrated functional CD27+ pro-B cells in FL and BM that may identify a predominantly fetal, B-cell lineage in humans.