Both mutated and unmutated memory B cells accumulate mutations in the course of the secondary response and develop a new antibody repertoire optimally adapted to the secondary stimulus

Tomohiro Kaji, Koji Furukawa, Akiko Ishige, Itsumi Toyokura, Masaki Nomura, Mariko Okada, Yoshimasa Takahashi, Michiko Shimoda, Toshitada Takemori

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

High-affinity memory B cells are preferentially selected during secondary responses and rapidly differentiate into antibody-producing cells. However, it remains unknown whether only high-affinity, mutated memory B cells simply expand to dominate the secondary response or if in fact memory B cells with a diverse VH repertoire, including those with no mutations, accumulate somatic mutations to create a new repertoire through the process of affinity maturation. In this report, we took a new approach to address this question by analyzing the VH gene repertoire of IgG1+ memory B cells before and after antigen re-exposure in a host unable to generate IgG+ B cells. We show here that both mutated and unmutated IgG1+ memory B cells respond to secondary challenge and expand while accumulating somatic mutations in their VH genes in a stepwise manner. Both types of memory cells subsequently established a VH gene repertoire dominated by two major clonotypes, which are distinct from the original repertoire before antigen re-exposure. In addition, heavily mutated memory B cells were excluded from the secondary repertoire. Thus, both mutated and unmutated IgG1+ memory cells equally contribute to establish a new antibody repertoire through a dynamic process of mutation and selection, becoming optimally adapted to the recall challenge.

Original languageEnglish (US)
Pages (from-to)683-695
Number of pages13
JournalInternational Immunology
Volume25
Issue number12
DOIs
StatePublished - Dec 1 2013
Externally publishedYes

Keywords

  • Antibody repertoire
  • Memory B cells
  • Secondary response
  • Somatic hypermutation

ASJC Scopus subject areas

  • Immunology

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