Original Research ARTICLE
Evidence for shaping of L chain repertoire by structural selection
- 1Department of Mathematics and Gonda Brain Research Center, Bar-Ilan University, Israel
- 2Joseph Henry Laboratories, Princeton University, United States
- 3UMR8549 Laboratoire de physique théorique de l'ENS (LPTENS), France
- 4UMR8550 Laboratoire de physique statistique de l'ENS (LPS), France
The naïve immunoglobulin repertoire in the blood differs from the direct output of the rearrangement process. These differences stem from selection that affects the germline gene usage and the junctional nucleotides. A major complication obscuring the details of the selection mechanism in the heavy chain is the failure to properly identify the D germline and determine the nucleotide addition and deletion in the junction region. The selection affecting junctional diversity can however be studied in the light chain that has no D gene.
We use probabilistic and deterministic models to infer and disentangle generation and selection of the light chain, using large samples of light chains sequenced from healthy donors and transgenic mice. We have previously used similar models for the Beta chain of T-cell receptors and the heavy chain of immunoglobulins .
Selection is observed mainly in the CDR3. The CDR3 length and mass distributions are narrower after selection than before, indicating stabilizing selection for mid-range values. Within the CDR3, Proline and Cysteine undergo negative selection while Glycine undergoes positive selection. The results presented here suggest structural selection maintaining the size of the CDR3 within a limited range, and preventing turns in the CDR3 region.
Keywords: Deep sequencing, B cell receptor, L chain, selection, rearrangement
Received: 18 Feb 2018;
Accepted: 25 May 2018.
Edited by:Victor Greiff, University of Oslo, Norway
Reviewed by:Felix Breden, Simon Fraser University, Canada
Marcos Vieira, University of Chicago, United States
Copyright: © 2018 Toledano, Elhanati, Benichou, Aleksandra, Mora and Louzoun. 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) and the copyright owner 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: Prof. Yoram Louzoun, Bar-Ilan University, Department of Mathematics and Gonda Brain Research Center, Ramat Gan 52900, Israel, Ramat Gan, Israel, firstname.lastname@example.org