Clustering of pre-B cell integrins induces galectin-1-dependent pre-B cell receptor relocalization and activation.
Interactions between B cell progenitors and bone marrow stromal cells are essential for normal B cell differentiation. We have previously shown that an immune developmental synapse is formed between human pre-B and stromal cells in vitro, leading to the initiation of signal transduction from the pre-BCR. This process relies on the direct interaction between the pre-BCR and the stromal cell-derived galectin-1 (GAL1) and is dependent on GAL1 anchoring to cell surface glycosylated counterreceptors, present on stromal and pre-B cells. In this study, we identify alpha(4)beta(1) (VLA-4), alpha(5)beta(1) (VLA-5), and alpha(4)beta(7) integrins as major GAL1-glycosylated counterreceptors involved in synapse formation. Pre-B cell integrins and their stromal cell ligands (ADAM15/fibronectin), together with the pre-BCR and GAL1, form a homogeneous lattice at the contact area between pre-B and stromal cells. Moreover, integrin and pre-BCR relocalizations into the synapse are synchronized and require actin polymerization. Finally, cross-linking of pre-B cell integrins in the presence of GAL1 is sufficient for driving pre-BCR recruitment into the synapse, leading to the initiation of pre-BCR signaling. These results suggest that during pre-B/stromal cell synapse formation, relocalization of pre-B cell integrins mediated by their stromal cell ligands drives pre-BCR clustering and activation, in a GAL1-dependent manner.
Rossi
Benjamin
B
Centre d'Immunologie de Marseille-Luminy (CIML), Université de la Méditerranée, Case 906, 13288 Marseille Cedex 09, France.
Espeli
Marion
M
Schiff
Claudine
C
Gauthier
Laurent
L
D000199:Actins / Q000378:metabolism; D000911:Antibodies, Monoclonal / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D002449:Cell Aggregation / Q000276:immunology; D002450:Cell Communication / Q000276:immunology; D045744:Cell Line, Tumor; D018920:Coculture Techniques; D003432:Cross-Linking Reagents / Q000378:metabolism; D037483:Galectin 1 / Q000502:physiology*; D006412:Hematopoietic Stem Cells / Q000378:metabolism*; D006801:Humans; D016023:Integrins / Q000378:metabolism*; D008024:Ligands; D008562:Membrane Glycoproteins / Q000276:immunology / Q000378:metabolism*; D054420:Pre-B Cell Receptors; D011940:Receptor Aggregation / Q000276:immunology; D011947:Receptors, Antigen, B-Cell; D017154:Stromal Cells / Q000378:metabolism
D000199:Actins; D000911:Antibodies, Monoclonal; D003432:Cross-Linking Reagents; D037483:Galectin 1; D016023:Integrins; D008024:Ligands; D008562:Membrane Glycoproteins; D054420:Pre-B Cell Receptors; D011947:Receptors, Antigen, B-Cell