Kappa and lambda light chain germline genes are quite different from each other in a number of respects. However no one has previously studied whether human kappa and lambda genes have a different CDRL3 region.
Catherine Townsend has analysed the data that we obtained from sequencing cells in early B cell development in order to document differences between kappa and lambda genes and has found that the CDRL3 regions are very different. Most of the differences can be attributed to the character of the germline V and J genes that make up the gene. However, there are extra nucleotides added in this junction by the enzyme TdT (short for Terminal deoxynucleotidyl transferase) and these do contribute to the diversity. We also found that the action of TdT varies between different donors, but is the same for each donor for kappa, lambda, and heavy chain. So there may be variants of the enzyme with slightly differing levels of activity within the population.
The character of kappa versus lambda light chains.
This work was recently published
Catherine L. Townsend, Julie M.J. Laffy, Yu-Chang Wu, Joselli Silva O’Hare, Victoria Martin, David Kipling, Franca Fraternali, Deborah K. Dunn-Walters Significant differences in physicochemical properties of human immunoglobulin kappa and lambda CDR3 regions. Front. Immunol., 27 September 2016 http://journal.frontiersin.org/article/10.3389/fimmu.2016.00388/full
Data files of sequences used in this work, and the clustering script, are available here.
Also available is the CDR3 clustering script with example files. Clustering into gene families uses the CDR 3 regions and is based on Levenstein distance.
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