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Tsuguo Mizuochi
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Journal Articles
Michiko Shimoda, Toru Nakamura, Yoshimasa Takahashi, Hideki Asanuma, Shin-ichi Tamura, Takeshi Kurata, Tsuguo Mizuochi, Norihiro Azuma, Choemon Kanno, Toshitada Takemori
Journal:
Journal of Experimental Medicine
Journal of Experimental Medicine (2001) 194 (11): 1597–1608.
Published: 03 December 2001
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, C α. 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, C γ, 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 V H 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.
Journal Articles
Hitoshi Nagaoka, Yoshimasa Takahashi, Reiko Hayashi, Tohru Nakamura, Kumiko Ishii, Junichiro Matsuda, Atsuo Ogura, Yumiko Shirakata, Hajime Karasuyama, Tetsuo Sudo, Shin-Ichi Nishikawa, Takeshi Tsubata, Tsuguo Mizuochi, Toshihiko Asano, Hitoshi Sakano, Toshitada Takemori
Journal:
Journal of Experimental Medicine
Journal of Experimental Medicine (2000) 192 (2): 171–182.
Published: 10 July 2000
Abstract
Ras is essential for the transition from early B cell precursors to the pro-B stage, and is considered to be involved in the signal cascade mediated by pre-B cell antigen receptors. To examine the role of p21 ras in the late stage of B cell differentiation, we established transgenic mice (TG) expressing a dominant-inhibitory mutant of Ha-ras (Asn-17 Ha-ras ) in B lineage cells at high levels after the early B cell precursor stage. Expression of p21 Asn-17 Ha-ras was associated with a prominent reduction in the number of late pre-B cells, but had little effect on proliferation of early pre-B cells. Inhibition of p21 ras activity markedly reduced the life span of pre-B cells, due, at least in part, to downregulation of the expression of an antiapoptotic protein, Bcl-xL. Thus, the apparent role for p21 ras activity in pre-B cell survival may explain the decreased numbers of late pre-B cells in Asn-17 Ha-ras TG. Consistent with this possibility, overexpression of Bcl-2 in Asn-17 Ha-ras TG reversed the reduction in the number of late pre-B cells undergoing immunoglobulin light chain gene ( IgL ) rearrangement and progressing to immature B cells. These results suggest that p21 ras mediates effector pathways responsible for pre-B cell survival, which is essential for progression to the late pre-B and immature B stages.