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The pre-B-cell receptor: selector of fitting immunoglobulin heavy chains for the B-cell repertoire

Abstract

In this Opinion article, I address the role of the pre-B-cell receptor (pre-BCR) in the development of antigen-specific B cells in terms of immunoglobulin heavy chain (IgH) variable-region repertoire selection, precursor B-cell differentiation and proliferation, and IgH allelic exclusion. Comparisons with the role of the pre-T-cell receptor (pre-TCR) in T-cell development raise provocative questions. Why do B- and T-cell lineages both use a surrogate chain — the surrogate light chain and the pre-TCR α-chain, respectively — as a step to develop their repertoires of antigen-recognizing cells? What are the functions of the pre-BCR and pre-TCR in lymphocyte differentiation and antigen-receptor allelic exclusion? This article, together with the accompanying article by Harald von Boehmer, hopes to answer some of these questions.

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Figure 1: Genomic organization of surrogate -light-chain genes and hypothetical protein structure.
Figure 2: Cellular stages of surrogate-light-chain expression during B-cell development.
Figure 3: Proposed mechanism for the crosslinking of pre-B-cell receptors at the surface of large precursor-BII cells.
Figure 4: Signalling from two types of pre-B-cell receptor at the surface of large precursor BII cells.

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Acknowledgements

F.M. is supported by the Swiss National Science Foundation.

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Entrez Gene

λ5

IgH

IgL

VpreB1

VpreB2

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Melchers, F. The pre-B-cell receptor: selector of fitting immunoglobulin heavy chains for the B-cell repertoire. Nat Rev Immunol 5, 578–584 (2005). https://doi.org/10.1038/nri1649

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