The Journal of Experimental Medicine
Aegean Conferences: 2009 Conferences
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Published 3 December 2001. doi:10.1084/jem.194.11.1597
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© Rockefeller University Press, 0022-1007/2001/12/1597/ $5.00
The Journal of Experimental Medicine, Volume 194, Number 11, December 3, 2001 1597-1608

Original Article

Isotype-specific Selection of High Affinity Memory B Cells in Nasal-associated Lymphoid Tissue

Michiko Shimoda1, Toru Nakamura2, Yoshimasa Takahashi2, Hideki Asanuma3, Shin-ichi Tamura3, Takeshi Kurata3, Tsuguo Mizuochi4, Norihiro Azuma1, Choemon Kanno1 and Toshitada Takemori2

1 Department of Applied Biochemistry, Utsunomiya University, Tochigi 321-8505, Japan
2 Department of Immunology, National Institute of Infectious Diseases, Tokyo 162-8640, Japan
3 Department of Pathology, National Institute of Infectious Diseases, Tokyo 162-8640, Japan
4 Laboratory of Biomedical Research, Department of Applied Biochemistry, Tokai University, Kanagawa 259-1292, Japan

Address correspondence to Toshitada Takemori, Dept. of Immunology, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8640, Japan. Phone: 03-5285-1111 ext. 2102; Fax: 03-5285-1156; E-mail: ttoshi{at}nih.go.jp

Mucosal immunoglobulin (Ig)A dominance has been proposed to be associated with preferential class switch recombination (CSR) to the IgA heavy chain constant region, C{alpha}. 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 {gamma} 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, C{gamma}, 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.

Key Words: memory • affinity maturation • germinal center • IgA • NALT


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