Distinct cellular pathways select germlineencoded and somatically mutated antibodies into immunological memory

Tomohiro Kaji, Akiko Ishige, Masaki Hikida, Junko Taka, Atsushi Hijikata, Masato Kubo, Takeshi Nagashima, Yoshimasa Takahashi, Tomohiro Kurosaki, Mariko Okada, Osamu Ohara, Klaus Rajewsky, Toshitada Takemori

Research output: Contribution to journalArticlepeer-review

179 Citations (Scopus)

Abstract

One component of memory in the antibody system is long-lived memory B cells selected for the expression of somatically mutated, high-affinity antibodies in the T cell-dependent germinal center (GC) reaction. A puzzling observation has been that the memory B cell compartment also contains cells expressing unmutated, low-affinity antibodies. Using conditional Bcl6 ablation, we demonstrate that these cells are generated through proliferative expansion early after immunization in a T cell-dependent but GC-independent manner. They soon become resting and long-lived and display a novel distinct gene expression signature which distinguishes memory B cells from other classes of B cells. GC-independent memory B cells are later joined by somatically mutated GC descendants at roughly equal proportions and these two types of memory cells efficiently generate adoptive secondary antibody responses. Deletion of T follicular helper (Tfh) cells significantly reduces the generation of mutated, but not unmutated, memory cells early on in the response. Thus, B cell memory is generated along two fundamentally distinct cellular differentiation pathways. One pathway is dedicated to the generation of high-affinity somatic antibody mutants, whereas the other preserves germ line antibody specificities and may prepare the organism for rapid responses to antigenic variants of the invading pathogen.

Original languageEnglish
Pages (from-to)2079-2097
Number of pages19
JournalJournal of Experimental Medicine
Volume209
Issue number11
DOIs
Publication statusPublished - 2012 Oct
Externally publishedYes

ASJC Scopus subject areas

  • Medicine(all)

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