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Science 316 (5822): 291-294

Copyright © 2007 by the American Association for the Advancement of Science

Structural Insight into Pre-B Cell Receptor Function

Alexander J. Bankovich,1 Stefan Raunser,6 Z. Sean Juo,2,3,4 Thomas Walz,6 Mark M. Davis,1,2,5 K. Christopher Garcia1,2,3,4*

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 {lambda}5 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.

1 Program in Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA.
2 Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA 94305, USA.
3 Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA 94305, USA.
4 Department of Structural Biology, Stanford University School of Medicine, Stanford, CA 94305, USA.
5 Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA.
6 Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.

* To whom correspondence should be addressed. E-mail: kcgarcia{at}

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