Differences in potential for amino acid change after mutation reveals distinct strategies for κ and λ light-chain variation

Uri Hershberg, Mark J. Shlomchik

Research output: Contribution to journalArticlepeer-review


B cells generate varied yet functional clones under high rates of mutation of their V genes. It has been proposed that as a result of the opposing demands of diversification and preservation of integrity, the V genes of heavy and light chains have evolved to overexpress codons prone to amino acid change in their complementarity determining regions (CDR) compared with the framework (FW) regions. We have analyzed the germ-line V genes of heavy and light chains (both κ and λ), comparing codons of CDR and FW of the germ-line V regions both to each other and to control regions. We found that in both germ-line heavy chains and λ chains, CDR codons are prone to replacement mutations, whereas in the FW, the opposite is true. Furthermore, the difference between CDR and FW in heavy chains and λ chains is based on codons that are prone to nonconservative changes of amino acid. In contrast, in germ-line κ chains, the codons in both CDR and FW are more prone to replacement mutations. We also demonstrated that negative selection during immune responses is more sensitive to nonconservative amino acid substitutions than overall amino acid change, demonstrating the applicability of our analysis to real-time process of selection in the immune system. The differences in germ-line κ and λ light chains' potential reaction to mutation suggests that via these two differently evolved light-chain types, the B cell repertoire encompasses two different strategies to balance diversity and stability in an immune response.

Original languageEnglish
Pages (from-to)15963-15968
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number43
StatePublished - 24 Oct 2006
Externally publishedYes


  • Affinity maturation
  • B cells
  • Codon usage
  • Evolution
  • Selection

ASJC Scopus subject areas

  • General


Dive into the research topics of 'Differences in potential for amino acid change after mutation reveals distinct strategies for κ and λ light-chain variation'. Together they form a unique fingerprint.

Cite this