B-cell extrinsic CR1/CR2 promotes natural antibody production and tolerance induction of anti-alphaGAL-producing B-1 cells

Blood. 2007 Feb 15;109(4):1773-81. doi: 10.1182/blood-2006-02-002386. Epub 2006 Oct 5.


B-1b cells produce IgM natural antibodies against alpha1-3Galbeta1-4GlcNAc (alphaGal). These can be tolerized by nonmyeloablative induction of mixed chimerism using alphaGal-positive (alphaGal+) donor marrow. We assessed the role of CR1/2 in this model for induction of tolerance of B-1b cells. Mixed hematopoietic chimerism was induced in alpha1-3galactosyltransferase (GalT-/-) and GalT-/-Cr2-/- mice with alphaGal+ BALB/c marrow donors. Anti-alphaGal Ab and anti-alphaGal Ab-producing B cells became undetectable in GalT-/- chimeras, whereas they persisted in chimeric GalT-/-Cr2-/- mice. To determine whether CR1/2 expression on stromal cells and/or hematopoietic cells was critical for B-1-cell tolerance, we generated GalT-/- radiation chimeras in which CR1/CR2 was expressed on either stromal cells, hematopoietic cells, neither, or both. After induction of mixed chimerism from alphaGal+ allogeneic bone marrow (BM) donors, anti-alphaGal-producing B cells were rendered tolerant in reconstituted recipients expressing only stromal CR1/CR2. Our results suggest a possible role for follicular dendritic cells that pick up immune complexes via CR1/CR2 receptors in the tolerization of B-1b cells.

Publication types

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

MeSH terms

  • Animals
  • Antibodies*
  • Antibody Formation*
  • B-Lymphocytes / immunology*
  • Bone Marrow Transplantation
  • Hematopoietic Stem Cells
  • Immune Tolerance / immunology*
  • Immunoglobulin M
  • Mice
  • Mice, Knockout
  • Receptors, Complement 3b / immunology*
  • Receptors, Complement 3b / physiology
  • Receptors, Complement 3d / immunology*
  • Receptors, Complement 3d / physiology
  • Stromal Cells
  • Transplantation Chimera
  • Trisaccharides / immunology*


  • Antibodies
  • Immunoglobulin M
  • Receptors, Complement 3b
  • Receptors, Complement 3d
  • Trisaccharides
  • alpha-galactosyl epitope