B cell selection and affinity maturation during an antibody response in the mouse with limited B cell diversity

Naoki Kanayama, Takafumi Kimoto, Kagefumi Todo, Yumiko Nishikawa, Masaki Hikida, Masaki Magari, Marilia Cascalho, Hitoshi Ohmori

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Abstract

The quasi-monoclonal mouse has limited B cell diversity, whose major (∼80%) B cell Ag receptors are comprised of the knockin VH 17.2.25 (VHT)-encoded H chain and the λ1 or λ2 L chain, thereby being specific for 4-hydroxy-3-nitrophenylacetyl. The p-nitrophenylacetyl (pNP) was found to be a low affinity analog of nitrophenylacetyl. We examined affinity maturation of anti-pNP IgG by analyzing mAbs obtained from quasi-monoclonal mice that were immunized with this low affinity Ag. The results are: 1) Although VHT/λ1 and VHT/λ2 IgM were equally produced, VHT/λ2 IgG almost exclusively underwent affinity maturation toward pNP. 2) A common mutation in complementarity-determining region 3 of VHT (T313A) mainly contributed to generating the specificity for pNP. 3) Because mutated VHT-encoded γ-chains could form λ1-bearing IgG in Chinese hamster ovary cells, apparent absence of VHT/λ1 anti-pNP IgG may not be due to the incompatibility between the γ-chains and the λ1-chain, but may be explained by the fact that VHT/λ1 B cells showed 50- to 100-fold lower affinity for pNP than VHT/λ2 B cells. 4) Interestingly, a pNP-specific IgM mAb that shared common mutations including T313A with high affinity anti-pNP IgG was isolated, suggesting that a part of hypermutation coupled with positive selection can occur before isotype switching. Thus, even weak B cell receptor engagement can elicit an IgM response, whereas only B cells that received signals stronger than a threshold may be committed to an affinity maturation process.

Original languageEnglish
Pages (from-to)6865-6874
Number of pages10
JournalJournal of Immunology
Volume169
Issue number12
Publication statusPublished - Dec 15 2002

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ASJC Scopus subject areas

  • Immunology

Cite this

Kanayama, N., Kimoto, T., Todo, K., Nishikawa, Y., Hikida, M., Magari, M., Cascalho, M., & Ohmori, H. (2002). B cell selection and affinity maturation during an antibody response in the mouse with limited B cell diversity. Journal of Immunology, 169(12), 6865-6874.