Access through your institution Buy or subscribe Somatic hyperpointmutation of antibody variable-region genes was the first mechanism of receptor modification to be discovered. It operates

in T-cell-dependent antibody responses during proliferative expansion of the responding B cells in a particular microenvironment, the germinal centre. From the newly arising antibody

mutants, those that show a high affinity for the immunizing antigen are selected into the ‘memory’ B-cell pool10. A second process by which B cells can change receptor specificity is based

on ‘secondary’ _V_ (_D_ )_J_ rearrangements. Each newborn B cell expresses a distinct antigen receptor, with a distinct combination of a _V_ H, a _D_ Hand a _J_ Hgene segment for the

segment initially expressed. It can then express a new κ chain, or switch to expression of a λ chain. This is achieved either by rearrangements of upstream (non-rearranged) _V_ κ genes to

downstream (non-rearranged) _J_ κ segments (Fig. 1), or by elimination of the _V_ κ_J_ κ rearrangement carried by the cell, together with the κ constant-region gene on the same chromosome.

Even in the case of the heavy chain, B cells can change specificity by rearranging a (non-rearranged) upstream _V_ Hgene into the _V_ H _D_ H _J_ Hcomplex that was initially assembled and

expressed10. This is a preview of subscription content, access via your institution ACCESS OPTIONS Access through your institution Subscribe to this journal Receive 51 print issues and

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which are calculated during checkout ADDITIONAL ACCESS OPTIONS: * Log in * Learn about institutional subscriptions * Read our FAQs * Contact customer support REFERENCES * Burnet, F. M. _The

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references AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Institute for Genetics, University of Köln, Weyertal 121, D-50931, Köln, Germany Klaus Rajewsky * EMBL Mouse Biology Programme, Via

Ramarini 32, I-00016, Monterotondo-Scalo (Rome), Italy Klaus Rajewsky Authors * Klaus Rajewsky 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 Rajewsky, K. Burnet's unhappy hybrid. _Nature_ 394, 624–625 (1998). https://doi.org/10.1038/29187 Download

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