September 5, 2013

The shape of the lymphocyte receptor repertoire: lessons from the B cell receptor





  • School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, NSW, Australia
Both the B cell receptor (BCR) and the T cell receptor (TCR) repertoires are generated through essentially identical processes of V(D)J recombination, exonuclease trimming of germline genes, and the random addition of non-template encoded nucleotides. The naïve TCR repertoire is constrained by thymic selection, and TCR repertoire studies have therefore focused strongly on the diversity of MHC-binding complementarity determining region (CDR) CDR3. The process of somatic point mutations has given B cell studies a major focus on variable (IGHV, IGLV, and IGKV) genes. This in turn has influenced how both the naïve and memory BCR repertoires have been studied. Diversity (D) genes are also more easily identified in BCR VDJ rearrangements than in TCR VDJ rearrangements, and this has allowed the processes and elements that contribute to the incredible diversity of the immunoglobulin heavy chain CDR3 to be analyzed in detail. This diversity can be contrasted with that of the light chain where a small number of polypeptide sequences dominate the repertoire. Biases in the use of different germline genes, in gene processing, and in the addition of non-template encoded nucleotides appear to be intrinsic to the recombination process, imparting “shape” to the repertoire of rearranged genes as a result of differences spanning many orders of magnitude in the probabilities that different BCRs will be generated. This may function to increase the precursor frequency of naïve B cells with important specificities, and the likely emergence of such B cell lineages upon antigen exposure is discussed with reference to public and private T cell clonotypes.


Keywords: BCR repertoire, TCR repertoire, V(D)J recombination, public clonotypes, private clonotypes, combinatorial diversity, junctional diversity
Citation: Jackson KJL, Kidd MJ, Wang Y and Collins AM (2013) The shape of the lymphocyte receptor repertoire: lessons from the B cell receptor. Front. Immunol. 4:263. doi: 10.3389/fimmu.2013.00263
Received: 31 May 2013; Accepted: 19 August 2013;
Published online: 02 September 2013.
Edited by:
Ramit Mehr, Bar-Ilan University, Israel
Reviewed by:
Ramit Mehr, Bar-Ilan University, Israel
Gur Yaari, Yale University, USA
Nir Friedman, Weizmann Institute of Science, Israel
Copyright: © 2013 Jackson, Kidd, Wang and Collins. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Katherine J. L. Jackson, School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, NSW 2052, Australia e-mail: katherine.jackson@unsw.edu.au

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