title: Adult BM generates CD5+ B1 cells containing abundant N-region additions.
abstract: 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.
authors.affiliation: Department of Pathology, Boston University School of Medicine, Boston, MA, USA.
authors.forename: Nichol E
authors.initials: NE
authors.lastname: Holodick
authors.forename: Karen
authors.initials: K
authors.lastname: Repetny
authors.forename: Xuemei
authors.initials: X
authors.lastname: Zhong
authors.forename: Thomas L
authors.initials: TL
authors.lastname: Rothstein
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D016175:B-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D001854:Bone Marrow Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D018956:CD5 Antigens / Q000276:immunology / Q000378:metabolism; D002273:Carcinogens / Q000494:pharmacology; D007136:Immunoglobulins / Q000096:biosynthesis / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010703:Phorbol Esters / Q000494:pharmacology
chemical_list: D018956:CD5 Antigens; D002273:Carcinogens; C526836:Cd5 protein, mouse; D007136:Immunoglobulins; D010703:Phorbol Esters