Adult BM generates CD5( ) B1 cells containing abundant N-region additions

作者:Holodick Nichol E; Repetny Karen; Zhong Xuemei; Rothstein Thomas L*
来源:European Journal of Immunology, 2009, 39(9): 2383-2394.
DOI:10.1002/eji.200838920

摘要

The self-renewing capacity of B1 cells infers homeostatic regulation; however, previous work suggests the low level of N-region addition characterizing B1 cells early in life increases with age, which implies that the B1-cell population is not a closed system. To explore this, we evaluated N-region addition in CD5( ) B1 cells generated from adult BM. Adult BM cells were marked with GFP introduced by mouse stem cell virus transduction, and were then adoptively transferred into lethally irradiated recipients. Within 2-3 months, we found GFP-marked CD5( ) B cells in the peritoneal cavities of recipients, which we demonstrate here meet a variety of criteria for B1-cell traits including Mac-1 surface expression; annexin, elfin, and Pax-5 gene expression; mitogenic responsiveness to phorbol ester; and spontaneous immunoglobulin secretion. Notably, we found by single-cell PCR that this population of BM-derived CD5( ) B1 cells expressed immunoglobulin with abundant N-region addition (and little V(H)11/V(H)12 skewing), unlike CD5( ) B1 cells obtained from unmanipulated animals but reminiscent of B2 cells. Further, we confirmed that native CD5( ) B1 cells from older mice contain more N-region additions than native CD5 B1 cells from younger mice. These results suggest that adult BM progenitors contribute to the peritoneal CD5( ) B1-cell pool over time.