Defective genes at checkpoints

Access through your institution Buy or subscribe During B-cell development in the bone marrow, a diverse repertoire of B-cell receptors (BCRs) is generated through the random rearrangement

of immunoglobulin gene segments. Many of these rearrangements result in BCRs that bind self antigens. However, such autoreactive B cells do not usually reach the periphery, because

intracellular signalling through a self-reactive BCR results in cell death, anergy or receptor editing (in which new rearrangements generate a modified BCR). To study how these tolerance

mechanisms might break down and lead to SLE, Kumar _et al_. investigated the _Sle1_ locus, which is known to be an SLE-susceptibility locus in mice and has an orthologue in humans. The

authors show that inherited differences in one of the genes encoded in this region, _Ly108_, result in variations in BCR signalling: the presence of _Sle1b__z_, an allele that is present in

a strain of SLE-prone mice, reduces the ability of self-reactive B cells to undergo anergy or receptor editing and therefore increases the number of self-reactive B cells in the periphery.

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Kumar, K. R. et al. Regulation of B cell tolerance by the lupus susceptibility gene _Ly108_. _Science_ 312, 1665–1669 (2006) Article  CAS  Google Scholar  * Pisitkun, P. et al. Autoreactive

B cell responses to RNA-related antigens due to _TLR7_ gene duplication. _Science_ 312, 1669–1672 (2006) Article  CAS  Google Scholar  FURTHER READING * Goodnow, C. C. Discriminating microbe

from self suffers a double Toll. _Science_ 312, 1606–1608 (2006) Article  Google Scholar  Download references Authors * Davina Dadley-Moore View author publications You can also search for

this author inPubMed Google Scholar RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Dadley-Moore, D. Defective genes at checkpoints. _Nat Rev Immunol_ 6,

571 (2006). https://doi.org/10.1038/nri1914 Download citation * Issue Date: 01 August 2006 * DOI: https://doi.org/10.1038/nri1914 SHARE THIS ARTICLE Anyone you share the following link with

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