2002 Fiscal Year Final Research Report Summary
Analysis and application of the capability of immune system to improve antigen-specificity of antibodies.
| Project/Area Number |
12450334
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
生物・生体工学
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| Research Institution | Okayama University |
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Principal Investigator |
OHMORI Hitoshi Okayama University, Biotechnology, Professor, 工学部, 教授 (70116440)
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| Co-Investigator(Kenkyū-buntansha) |
KANAYAMA Naoki Okayama University, Biotechnology, Lecturer, 工学部, 講師 (70304334)
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| Project Period (FY) |
2000 – 2002
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| Keywords | Antibody / antibody genes / affinity maturation / somatic mutation / transgenic mouse / B lymphocytes / germinal center / gene rearrangement |
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| Research Abstract |
Recently, peripheral B cells have been shown to undergo secondary V(D)J rearrangement of Ig genes, but the physiological role of this event has not been fully elucidated. Here, we investigated whether rearrangement of L chain genes in the periphery is involved in the generation of high-affinity Abs. To test this possibility, we used a 17.2.25 rearranged VHDJH gene (VHT)-knockin mouse whose B cell diversity is limited due to the expression of the site-directed transgene. Immunization of the mouse with p-nitrophenylacetyl (pNP)-conjugated chicken γ-globulin (CGG) preferentially led to the production of anti-pNP IgG Abs comprised of non-VHT-encoded H chains and λ chains, which constituted a majority of high-affinity IgG to this hapten. We isolated three independent anti-pNP IgG1 mAbs (two bearing λ1 with high-affinity and one bearing κ with low-affinity), all of which used a common VHDJH containing an identical point mutation, thus suggesting that κ to λ1 replacement contributed to an increase of the Ab affinity. RAG-2 mRNA and the recombination signal sequence break reflecting the λ1 gene rearrangement were detected in the draining lymph node (LN) of immunized mice, but not of non-immunized animals. There was a close correlation between the levels of the λ gene rearrangement and λ^+ high-affinity anti-pNP IgG. Thus, our findings suggest that new rearrangement of λ genes in the periphery contributes to affinity maturation of anti-pNP IgG.
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[Publications] Magari, M., Sawatari, T., Kawao, Y., Cascalho, M., Wabl. M., Kanayama, N., Hikida, M., Ohmori, H.: "Contribution of L chain rearrangement in peripheral B cells to the generation of high-affinity antibodies"Eur. J. Immunol.. 32(3). 956-966 (2002)
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[Publications] Kanayama, N., Kimoto, T., Todo, K., Nishikawa, Y., Hikida, M., Magari, M., Cascalho, M., Ohmori, R.: "B cell selection and affinity maturation during an antibody response in the mouse with limited B cell diversity"J. Immunol.. 169(24). 6865-6874 (2002)
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[Publications] Kanayama, N., Hukue, C., Magari, M., Ohtani, K., Hikida, M., Yamada, M., Matsuda, S., Ohmori, H.: "Use of secondarily revised VH genes in IgE antibodies produced in mice infected with the nematode Nippostrongylus brasiliensis"Immunol. Lett.. 77(4). 181-186 (2001)
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「研究成果報告書概要(欧文)」より
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