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

Abstract

B-1b cells produce IgM natural antibodies against α1-3Galβ1- 4GlcNAc (αGAL). These can be tolerized by nonmyeloablative induction of mixed chimerism using αGAL-positive (αGAL+) 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 α1- 3galactosyltransferase (GalT-/-) and GalT-/-Cr2 -/- mice with αGAL+ BALB/c marrow donors. Anti-αGAL Ab and anti-αGAL 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 αGAL+ allogeneic bone marrow (BM) donors, anti-αGAL-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. © 2007 by The American Society of Hematology.