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

B-1b cells produce IgM natural antibodies against 1-3Gal 1-4GlcNAc ( Gal). These can be tolerized by nonmyeloablative induction of mixed chimerism using Galpositive ( Gal ) 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 1-3galactosyltransferase (GalT / ) and GalT / Cr2 / mice with Gal BALB/c marrow donors. AntiGal Ab and antiGal 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 Gal allogeneic bone marrow (BM) donors, antiGal–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. (Blood. 2007;109:1773-1781)