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

Eur J Immunol. 2009 Sep;39(9):2383-94. doi: 10.1002/eji.200838920.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adoptive Transfer
  • Animals
  • B-Lymphocyte Subsets / drug effects
  • B-Lymphocyte Subsets / immunology*
  • B-Lymphocyte Subsets / metabolism
  • Bone Marrow Cells / drug effects
  • Bone Marrow Cells / immunology*
  • Bone Marrow Cells / metabolism
  • CD5 Antigens / immunology
  • CD5 Antigens / metabolism
  • Carcinogens / pharmacology
  • Immunoglobulins / biosynthesis
  • Immunoglobulins / immunology
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Phorbol Esters / pharmacology

Substances

  • CD5 Antigens
  • Carcinogens
  • Cd5 protein, mouse
  • Immunoglobulins
  • Phorbol Esters