title: Ig alpha/Ig beta complexes generate signals for B cell development independent of selective plasma membrane compartmentalization.
abstract: Ligand-induced BCR association with detergent-resistant plasma membrane compartments (lipid rafts) has been argued to be essential for initiating and/or sustaining Igalpha/Igbeta-dependent BCR signaling. Because a fraction of the BCR and an even larger fraction of the preBCR associates with lipid rafts in the apparent absence of ligand stimulation, it has been proposed that raft-associated receptor complexes mediate the ligand-independent basal signaling events observed in resting B lineage cells. However, there is no direct evidence that localization of Igalpha/Igbeta-containing complexes to detergent-resistant membrane compartments is absolutely required for the signaling events that drive B cell development. To address these issues we have designed surrogate preBCR/Igalpha/Igbeta complexes that are incapable of ligand-induced aggregation and that are preferentially targeted to either raft or nonraft compartments. An analysis of their ability to promote the preBCR-dependent proB-->preB cell transition of murine B cell progenitors revealed that expression of these surrogate receptor complexes at levels that approximate that of the conventional preBCR can drive B cell development in a manner independent of both aggregation and lipid raft localization.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
authors.forename: Ezequiel M
authors.initials: EM
authors.lastname: Fuentes-Pananá
authors.forename: Gregory
authors.initials: G
authors.lastname: Bannish
authors.forename: Dustin
authors.initials: D
authors.lastname: van der Voort
authors.forename: Leslie B
authors.initials: LB
authors.lastname: King
authors.forename: John G
authors.initials: JG
authors.lastname: Monroe
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D016175:B-Lymphocyte Subsets / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D051925:CD79 Antigens; D002451:Cell Compartmentation / Q000235:genetics / Q000276:immunology; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology*; D002460:Cell Line; D003902:Detergents; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics; D021962:Membrane Microdomains / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D054420:Pre-B Cell Receptors; D011947:Receptors, Antigen, B-Cell / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D017384:Sequence Deletion; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology*; D012995:Solubility
chemical_list: D015703:Antigens, CD; D051925:CD79 Antigens; C497882:Cd79a protein, mouse; C497884:Cd79b protein, mouse; D003902:Detergents; D008562:Membrane Glycoproteins; D054420:Pre-B Cell Receptors; D011947:Receptors, Antigen, B-Cell; D011993:Recombinant Fusion Proteins