Affinity maturation of B cells involves not only a few but a whole spectrum of relevant mutations

Armin A. Weiser, Nicole Wittenbrink, Lei Zhang, Andrej I. Schmelzer, Atijeh Valai, Michal Or-Guil

Research output: Contribution to journalArticleResearchpeer-review

8 Citations (Scopus)

Abstract

Affinity maturation of B lymphocytes within germinal centers involves both diversification of their B-cell receptors (BCRs) by somatic hypermutation (SHM) and a crucial receptor-mediated selection step. However, in contrast to recent advances in revealing the molecular mechanism of SHM, the fundamentals of the selection process are still poorly understood, i.e. it is often not clear how and how many mutations contribute to improving a BCR during the response against a given antigen. A general drawback in assessing the mutations relevant to the selection process is the difficult task of rating the relative contributions of selection and intrinsic biases to the experimentally observed mutation patterns of BCRs. The approach proposed here is premised on statistical comparison of the frequency distributions of nucleotide substitutions as observed in datasets of hypermutated BCRs against their frequency distribution expected under the null hypothesis of no selection. Thereby, we show that the spectrum of mutations relevant to maturation of canonical anti-(4-hydroxy-3-nitrophenyl)acetyl BCRs is much broader than previously acknowledged, going beyond the scope of single key mutations. Moreover, our results suggest that maturation not only involves selection by means of affinity but likewise expression and stabilization of BCRs. 

Original languageEnglish
Pages (from-to)345-356
Number of pages12
JournalInternational Immunology
Volume23
Issue number5
DOIs
Publication statusPublished - 2011
Externally publishedYes

Keywords

  • B-lymphocyte
  • Somatic hypermutation

Cite this