title: B-cell extrinsic CR1/CR2 promotes natural antibody production and tolerance induction of anti-alphaGAL-producing B-1 cells.
abstract: 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.
authors.affiliation: Bone Marrow Transplantation Section, Transplantation Biology Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, USA.
authors.forename: Ichiro
authors.initials: I
authors.lastname: Shimizu
authors.forename: Toshiyasu
authors.initials: T
authors.lastname: Kawahara
authors.forename: Fabienne
authors.initials: F
authors.lastname: Haspot
authors.forename: Philip D
authors.initials: PD
authors.lastname: Bardwell
authors.forename: Michael C
authors.initials: MC
authors.lastname: Carroll
authors.forename: Megan
authors.initials: M
authors.lastname: Sykes
mesh_terms: D000818:Animals; D000906:Antibodies; D000917:Antibody Formation; D001402:B-Lymphocytes / Q000276:immunology*; D016026:Bone Marrow Transplantation; D006412:Hematopoietic Stem Cells; D007108:Immune Tolerance / Q000276:immunology*; D007075:Immunoglobulin M; D051379:Mice; D018345:Mice, Knockout; D017463:Receptors, Complement 3b / Q000276:immunology* / Q000502:physiology; D017464:Receptors, Complement 3d / Q000276:immunology* / Q000502:physiology; D017154:Stromal Cells; D018183:Transplantation Chimera; D014312:Trisaccharides / Q000276:immunology*
chemical_list: D000906:Antibodies; D007075:Immunoglobulin M; D017463:Receptors, Complement 3b; D017464:Receptors, Complement 3d; D014312:Trisaccharides; C076569:alpha-galactosyl epitope