Interaction of murine precursor B cell receptor with stroma cells is controlled by the unique tail of lambda 5 and stroma cell-associated heparan sulfate.
Efficient clonal expansion of early precursor B (pre-B) cells requires signals delivered by an Ig-like integral membrane complex, the so-called pre-B cell receptor (pre-BCR). A pre-BCR consists of two membrane micro H chains, two covalently associated surrogate L chains, and the heterodimeric signaling transducer Igalphabeta. In contrast to a conventional Ig L chain, the surrogate L chain is a heterodimer composed of the invariant polypeptides VpreB and lambda5. Although it is still unclear how pre-BCR signals are initiated, two recent findings support a ligand-dependent initiation of pre-BCR signals: 1) a pre-BCR/galectin-1 interaction is required to induce phosphorylation of Igalphabeta in a human precursor B line, and 2) soluble murine as well as human pre-BCR molecules bind to stroma and other adherent cells. In this study, we show that efficient binding of a soluble murine pre-BCR to stroma cells requires the non-Ig-like unique tail of lambda5. Surprisingly however, a murine pre-BCR, in contrast to its human counterpart, does not interact with galectin-1, as revealed by lactose blocking, RNA interference, and immunoprecipitation assays. Finally, the binding of a murine pre-BCR to stroma cells can be blocked either with heparin or by pretreatment of stroma cells with heparitinase or a sulfation inhibitor. Hence, efficient binding of a murine pre-BCR to stroma cells requires the unique tail of lambda5 and stroma cell-associated heparan sulfate. These findings not only identified heparan sulfate as potential pre-BCR ligands, but will also facilitate the development of appropriate animal models to determine whether a pre-BCR/heparan sulfate interaction is involved in early B cell maturation.
Bradl
Harald
H
Division of Molecular Immunology, Department of Internal Medicine III, Nikolaus-Fiebiger-Center, University of Erlangen-Nürnberg, Glückstrasse 6, D-91054 Erlangen, Germany.
Wittmann
Jürgen
J
Milius
Doreen
D
Vettermann
Christian
C
Jäck
Hans-Martin
HM
D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D016367:Baculoviridae / Q000235:genetics; D001666:Binding Sites, Antibody / Q000187:drug effects / Q000235:genetics; D002460:Cell Line; D037483:Galectin 1 / Q000378:metabolism; D005822:Genetic Vectors; D006367:HeLa Cells; D006412:Hematopoietic Stem Cells / Q000276:immunology* / Q000378:metabolism*; D006493:Heparin / Q000494:pharmacology; D006497:Heparan Sulfate / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D007127:Immunoglobulin Constant Regions / Q000378:metabolism; D007147:Immunoglobulin Light Chains; D054444:Immunoglobulin Light Chains, Surrogate; D007135:Immunoglobulin Variable Region / Q000378:metabolism / Q000502:physiology*; D007146:Immunoglobulin lambda-Chains / Q000378:metabolism / Q000502:physiology*; D008024:Ligands; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary / Q000235:genetics; D011947:Receptors, Antigen, B-Cell / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000378:metabolism*; D012995:Solubility; D018411:Spodoptera; D017154:Stromal Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism
D037483:Galectin 1; D006493:Heparin; D006497:Heparan Sulfate; D007127:Immunoglobulin Constant Regions; D007147:Immunoglobulin Light Chains; D054444:Immunoglobulin Light Chains, Surrogate; D007135:Immunoglobulin Variable Region; D007146:Immunoglobulin lambda-Chains; D008024:Ligands; D008562:Membrane Glycoproteins; D011947:Receptors, Antigen, B-Cell