TY - JOUR
T1 - Isotype-specific selection of high affinity memory B cells in nasal-associated lymphoid tissue
AU - Shimoda, Michiko
AU - Nakamura, Toru
AU - Takahashi, Yoshimasa
AU - Asanuma, Hideki
AU - Tamura, Shin Ichi
AU - Kurata, Takeshi
AU - Mizuochi, Tsuguo
AU - Azuma, Norihiro
AU - Kanno, Choemon
AU - Takemori, Toshitada
PY - 2001/12/3
Y1 - 2001/12/3
N2 - 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.
AB - 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.
KW - Affinity maturation
KW - Germinal center
KW - IgA
KW - Memory
KW - NALT
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U2 - 10.1084/jem.194.11.1597
DO - 10.1084/jem.194.11.1597
M3 - Article
C2 - 11733574
AN - SCOPUS:0035803555
VL - 194
SP - 1597
EP - 1607
JO - Journal of Experimental Medicine
JF - Journal of Experimental Medicine
SN - 0022-1007
IS - 11
ER -