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 Blood, 15 February 2007, Vol. 109, No. 4, pp. 1773-1781.
Prepublished online as a Blood First Edition Paper on October 5, 2006; DOI 10.1182/blood-2006-02-002386.

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Submitted February 9, 2006
Accepted September 19, 2006

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

Ichiro Shimizu, Toshiyasu Kawahara, Fabienne Haspot, Philip Bardwell, Michael Carroll, and Megan Sykes*

Transplantation Biology Research Center, Massachusetts General Hospital, United States
Harvard Medical School, United States

* Corresponding author; email: megan.sykes{at}tbrc.mgh.harvard.edu.

B-1b cells produce IgM natural antibodies against {alpha}1-3G7{alpha}1{beta}1-4GlcNAc ({alpha}Gal). These can be tolerized by non-myeloablative induction of mixed chimerism using {alpha}Gal-positive 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 {alpha}1-3-galactosyltransferase (GalT-/-) and GalT-/-Cr2-/- mice with {alpha}Gal+ BALB/c marrow donors. Anti-{alpha}Gal Ab and anti-{alpha}Gal 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 {alpha}Gal+ allogeneic bone marrow (BM) donors, anti-{alpha}Gal-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.


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