Abstract
The pre-B cell receptor (pre-BCR) serves as a checkpoint in B cell development. In the 2.7 angstrom structure of a human pre-BCR Fab-like fragment, consisting of an antibody heavy chain (HC) paired with the surrogate light chain, the "unique regions" of VpreB and lambda5 replace the complementarity-determining region 3 (CDR3) loop of an antibody light chain and appear to "probe" the HC CDR3, potentially influencing the selection of the antibody repertoire. Biochemical analysis indicates that the pre-BCR is impaired in its ability to recognize antigen, which, together with electron microscopic visualization of a pre-BCR dimer, suggests ligand-independent oligomerization as the likely signaling mechanism.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Complementarity Determining Regions / chemistry
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Complementarity Determining Regions / physiology
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Crystallography, X-Ray
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Humans
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Immunoglobulin Heavy Chains / chemistry
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Immunoglobulin Heavy Chains / physiology
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Immunoglobulin Light Chains / chemistry
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Immunoglobulin Light Chains / physiology
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Immunoglobulin Light Chains, Surrogate
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Membrane Glycoproteins / chemistry*
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Membrane Glycoproteins / physiology
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Membrane Glycoproteins / ultrastructure
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Mice
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Models, Molecular
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Pre-B Cell Receptors
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Protein Conformation
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Receptors, Antigen, B-Cell / chemistry*
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Receptors, Antigen, B-Cell / physiology
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Receptors, Antigen, B-Cell / ultrastructure
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Recombinant Proteins
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Structure-Activity Relationship
Substances
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Complementarity Determining Regions
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Immunoglobulin Heavy Chains
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Immunoglobulin Light Chains
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Immunoglobulin Light Chains, Surrogate
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Membrane Glycoproteins
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Pre-B Cell Receptors
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Receptors, Antigen, B-Cell
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Recombinant Proteins