Submitted January 8, 2009
Accepted March 17, 2009
Impaired B cell development at the pre-BII cell stage in galectin-1 deficient mice due to inefficient pre-BII-stromal cell interactions
Marion Espeli, Stephane J.C. Mancini*, Caroline Breton, Francoise Poirier, and Claudine Schiff
Centre d'Immunologie de Marseille-Luminy, Universite de la Mediterranee, Marseille, France
Institut National de la Sante et de la Recherche Medicale (INSERM), U631, Marseille, France
Centre National de la Recherche Scientifique (CNRS), UMR6102, Marseille, France
Institut Jacques Monod, CNRS UMR 7592, Paris, France
* Corresponding author; email: mancini{at}ciml.univ-mrs.fr.
Activation of the pre-B cell receptor (pre-BCR) in the bone marrow depends on both tonic and ligand-induced signaling and leads to pre-BII cell proliferation and differentiation. Using normal mouse bone marrow pre-BII cells, we demonstrate that the ligand-induced pre-BCR activation depends on pre-BCR/galectin-1/integrin interactions leading to pre-BCR clustering at the pre-BII/stromal cell synapse. In contrast, heparan sulfates, shown to be pre-BCR ligands in mice, are not implicated in pre-BCR relocalization. Inhibition of pre-BCR/ galectin-1/integrin interactions has functional consequences, since pre-BII cell proliferation and differentiation are impaired in an in vitro B cell differentiation assay, without affecting cellular apoptosis. Most strikingly, although galectin-1 deficient mice do not show an apparent B cell phenotype, the kinetics of de novo B cell reconstitution after hydroxyurea-treatment indicates a specific delay in pre-BII cell recovery due to a decrease in pre-BII cell differentiation and proliferation. Thus, although it remains possible that the pre-BCR interacts with other ligands, these results highlight the role played by the stromal cell-derived galectin-1 for the efficient development of normal pre-BII cells and suggest the existence of pre-BII specific stromal cell niches in normal bone marrow.
