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

Research output: Contribution to journalArticle

19 Citations (Scopus)

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

Fingerprint

Antibody Formation
B-Lymphocytes
Immunoglobulin G
Immunoglobulin M
Immunoglobulin Class Switching
Complementarity Determining Regions
Mutation
Cricetulus
Ovary

ASJC Scopus subject areas

  • Immunology

Cite this

B cell selection and affinity maturation during an antibody response in the mouse with limited B cell diversity. / Kanayama, Naoki; Kimoto, Takafumi; Todo, Kagefumi; Nishikawa, Yumiko; Hikida, Masaki; Magari, Masaki; Cascalho, Marilia; Ohmori, Hitoshi.

In: Journal of Immunology, Vol. 169, No. 12, 15.12.2002, p. 6865-6874.

Research output: Contribution to journalArticle

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, vol. 169, no. 12, pp. 6865-6874.
Kanayama, Naoki ; Kimoto, Takafumi ; Todo, Kagefumi ; Nishikawa, Yumiko ; Hikida, Masaki ; Magari, Masaki ; Cascalho, Marilia ; Ohmori, Hitoshi. / B cell selection and affinity maturation during an antibody response in the mouse with limited B cell diversity. In: Journal of Immunology. 2002 ; Vol. 169, No. 12. pp. 6865-6874.
@article{f4a32820c65e4adabdaa09fb97468d3c,
title = "B cell selection and affinity maturation during an antibody response in the mouse with limited B cell diversity",
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.",
author = "Naoki Kanayama and Takafumi Kimoto and Kagefumi Todo and Yumiko Nishikawa and Masaki Hikida and Masaki Magari and Marilia Cascalho and Hitoshi Ohmori",
year = "2002",
month = "12",
day = "15",
language = "English",
volume = "169",
pages = "6865--6874",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "12",

}

TY - JOUR

T1 - B cell selection and affinity maturation during an antibody response in the mouse with limited B cell diversity

AU - Kanayama, Naoki

AU - Kimoto, Takafumi

AU - Todo, Kagefumi

AU - Nishikawa, Yumiko

AU - Hikida, Masaki

AU - Magari, Masaki

AU - Cascalho, Marilia

AU - Ohmori, Hitoshi

PY - 2002/12/15

Y1 - 2002/12/15

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=0037114122&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0037114122&partnerID=8YFLogxK

M3 - Article

C2 - 12471119

AN - SCOPUS:0037114122

VL - 169

SP - 6865

EP - 6874

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 12

ER -