Control of the Sizes and Contents of Precursor B Cell Repertoires in Bone Marrow

  1. Gregory R. Bock Organizer and
  2. Jamie A. Goode
  1. Fritz Melchers

Published Online: 28 SEP 2007

DOI: 10.1002/9780470515280.ch12

Ciba Foundation Symposium 204 - The Molecular Basis of Cellular Defence Mechanisms

Ciba Foundation Symposium 204 - The Molecular Basis of Cellular Defence Mechanisms

How to Cite

Melchers, F. (2007) Control of the Sizes and Contents of Precursor B Cell Repertoires in Bone Marrow, in Ciba Foundation Symposium 204 - The Molecular Basis of Cellular Defence Mechanisms (eds G. R. Bock and J. A. Goode), John Wiley & Sons, Ltd., Chichester, UK. doi: 10.1002/9780470515280.ch12

Author Information

  1. Basel Institute for Immunology, Grenzacherstrasse 487, CH-4005 Basel, Switzerland

Publication History

  1. Published Online: 28 SEP 2007

ISBN Information

Print ISBN: 9780471965671

Online ISBN: 9780470515280

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Keywords:

  • precursor β cell repertoires;
  • bone marrow;
  • physiological roles;
  • β cell development;
  • H chain allelic exclusion

Summary

Ordered rearrangements of immunoglobulin (Ig) gene loci, first as DH to JH, then as VH to DHJH, and finally as VL to JL segment-specific recombinations occur ‘in-frame’ and ‘out-of-frame’. ‘In-frame’ rearrangements lead to the expression of truncated DHJH-µC proteins and to µH chains. These H chain proteins have two major effects on precursor B cells. They suppress (as DJCµ proteins) or enhance (as full µH chain) the proliferation of precursor cells at the point where these precursors express these proteins. At the same time, they signal allelic exclusion of the µH chain alleles, so that VH to DHJH rearrangement at the second allele is suppressed. Regulation of precursor B cell proliferation and H chain allelic exclusion is mediated by a pre-B cell receptor that is composed of the µH chains and a surrogate L chain. This surrogate L chain is made up of two proteins encoded by the Vpre-B and λ5 genes that are expressed only at the early precursor cell stages just before and when H chain genes are first expressed. They are not found in later B cell development, when L chains are expressed, nor in any other cell of the body tested so far. The physiological roles of surrogate L chain and of the pre-B receptor have been clarified by generating mutant mice in which the λ5 gene has been inactivated by targeted disruption. Molecular mechanisms and cellular developments, by which the pre-B receptor controls proliferation and allelic exclusion, are discussed.