Isotype-specific selection of high affinity memory B cells in nasal-associated lymphoid tissue

Michiko Shimoda, Toru Nakamura, Yoshimasa Takahashi, Hideki Asanuma, Shin Ichi Tamura, Takeshi Kurata, Tsuguo Mizuochi, Norihiro Azuma, Choemon Kanno, Toshitada Takemori

Research output: Contribution to journalArticle

57 Scopus citations

Abstract

Mucosal immunoglobulin (Ig)A dominance has been proposed to be associated with preferential class switch recombination (CSR) to the IgA heavy chain constant region, Ca. Here, we report that B cell activation in nasal-associated lymphoid tissue (NALT) upon stimulation with the hapten (4-hydroxy-3-nitrophenyl)acetyl (NP) coupled to chicken γ globulin caused an anti-NP memory response dominated by high affinity IgA antibodies. In the response, however, NP-specific IgG+ B cells expanded and sustained their number as a major population in germinal centers (GCs), supporting the view that CSR to IgG heavy chain constant region, Cγ, operated efficiently in NALT. Both IgG+ and IgA+ GC B cells accumulated somatic mutations, indicative of affinity maturation to a similar extent, suggesting that both types of cell were equally selected by antigen. Despite the selection in GCs, high affinity NP-specific B cells were barely detected in the IgG memory compartment, whereas such cells dominated the IgA memory compartment. Taken together with the analysis of the VH gene clonotype in GC and memory B cells, we propose that NALT is equipped with a unique machinery providing IgA-specific enrichment of high affinity cells into the memory compartment, facilitating immunity with high affinity and noninflammatory secretory antibodies.

Original languageEnglish (US)
Pages (from-to)1597-1607
Number of pages11
JournalJournal of Experimental Medicine
Volume194
Issue number11
DOIs
StatePublished - Dec 3 2001
Externally publishedYes

Keywords

  • Affinity maturation
  • Germinal center
  • IgA
  • Memory
  • NALT

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Shimoda, M., Nakamura, T., Takahashi, Y., Asanuma, H., Tamura, S. I., Kurata, T., Mizuochi, T., Azuma, N., Kanno, C., & Takemori, T. (2001). Isotype-specific selection of high affinity memory B cells in nasal-associated lymphoid tissue. Journal of Experimental Medicine, 194(11), 1597-1607. https://doi.org/10.1084/jem.194.11.1597