title: Structural basis for galectin-1-dependent pre-B cell receptor (pre-BCR) activation.
abstract: During B cell differentiation in the bone marrow, the expression and activation of the pre-B cell receptor (pre-BCR) constitute crucial checkpoints for B cell development. Both constitutive and ligand-dependent pre-BCR activation modes have been described. The pre-BCR constitutes an immunoglobulin heavy chain (Igμ) and a surrogate light chain composed of the invariant λ5 and VpreB proteins. We previously showed that galectin-1 (GAL1), produced by bone marrow stromal cells, is a pre-BCR ligand that induces receptor clustering, leading to efficient pre-BII cell proliferation and differentiation. GAL1 interacts with the pre-BCR via the unique region of λ5 (λ5-UR). Here, we investigated the solution structure of a minimal λ5-UR motif that interacts with GAL1. This motif adopts a stable helical conformation that docks onto a GAL1 hydrophobic surface adjacent to its carbohydrate binding site. We identified key hydrophobic residues from the λ5-UR as crucial for the interaction with GAL1 and for pre-BCR clustering. These residues involved in GAL1-induced pre-BCR activation are different from those essential for autonomous receptor activation. Overall, our results indicate that constitutive and ligand-induced pre-BCR activation could occur in a complementary manner.
authors.affiliation: Laboratoire d'Ingénierie des Systèmes Macromoléculaires, CNRS UMR7255, Aix-Marseille Université, 13402 Marseille cedex 20, France.
authors.forename: Latifa
authors.initials: L
authors.lastname: Elantak
authors.forename: Marion
authors.initials: M
authors.lastname: Espeli
authors.forename: Annie
authors.initials: A
authors.lastname: Boned
authors.forename: Olivier
authors.initials: O
authors.lastname: Bornet
authors.forename: Jeremy
authors.initials: J
authors.lastname: Bonzi
authors.forename: Laurent
authors.initials: L
authors.lastname: Gauthier
authors.forename: Mikael
authors.initials: M
authors.lastname: Feracci
authors.forename: Philippe
authors.initials: P
authors.lastname: Roche
authors.forename: Françoise
authors.initials: F
authors.lastname: Guerlesquin
authors.forename: Claudine
authors.initials: C
authors.lastname: Schiff
mesh_terms: D001665:Binding Sites; D002454:Cell Differentiation; D002460:Cell Line; D049109:Cell Proliferation; D018360:Crystallography, X-Ray; D037483:Galectin 1 / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D054420:Pre-B Cell Receptors / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D054448:Precursor Cells, B-Lymphoid / Q000737:chemistry / Q000166:cytology / Q000378:metabolism*; D017154:Stromal Cells / Q000166:cytology / Q000378:metabolism
chemical_list: D037483:Galectin 1; D008024:Ligands; D054420:Pre-B Cell Receptors