Impaired B cell development at the pre-BII cell stage in galectin-1 deficient mice due to inefficient pre-BII-stromal cell interactions.

International audienceActivation 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