Analysis of marginal zone B cell development in the mouse with limited B cell diversity

Role of the antigen receptor signals in the recruitment of B cells to the marginal zone

Naoki Kanayama, Marilia Cascalho, Hitoshi Ohmori

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

The quasimonoclonal (QM) mouse provides an intelligible model to analyze the B cell selection as the competition between two major 4-hydroxy-3- nitrophenylacetyl-specific B cell populations whose BCR are comprised of the knockin VH17.2.25 (VHT)-encoded H chain and the λ1 or λ2 L chain. In this study, we show the QM system is useful to examine how BCR signals guide a subset of B cells to the marginal zone (MZ). Compared with the control C57BL/6 mice, the QM mice had ∼2.7-fold increased number of B cells exhibiting the MZ B cell phenotype and a larger MZ area in the spleen. Interestingly, VHT/λ2 B cells significantly predominated over VHT/λ1 B cells in MZ-(VHT/λ1:V HT/λ2 ≈ 3:7) and transitional 2-B cell subsets, while these two populations were comparable in immature, transitional 1, and mature counterparts. Thus, the biased use of λ2 in the MZ B cells may be the result of selection in the periphery. The enlargement of MZ B cell compartment and the preferred recruitment of the VHT/λ2 B cells were further augmented by doubling the VHT gene, but dampened by the dysfunction of Bruton's tyrosine kinase, suggesting a positive role of BCR signaling in this selection. Comparison of Ag specificity between V HT/λ1 and VHT/λ2 IgM mAbs revealed a polyreactive nature of the VHT/λ2 BCR, including the reactivity with ssDNA. Taken together, it is suggested that poly reactivity (including self-reactivity) of BCR is crucial in driving B cells to differentiate into the MZ phenotype.

Original languageEnglish
Pages (from-to)1438-1445
Number of pages8
JournalJournal of Immunology
Volume174
Issue number3
Publication statusPublished - Feb 1 2005

Fingerprint

Antigen Receptors
B-Lymphocytes
B-Lymphocyte Subsets
Phenotype
B-Lymphoid Precursor Cells
Inbred C57BL Mouse
Population
Immunoglobulin M
Spleen

ASJC Scopus subject areas

  • Immunology

Cite this

@article{87169a8c602f401e92aa8c2d0239e562,
title = "Analysis of marginal zone B cell development in the mouse with limited B cell diversity: Role of the antigen receptor signals in the recruitment of B cells to the marginal zone",
abstract = "The quasimonoclonal (QM) mouse provides an intelligible model to analyze the B cell selection as the competition between two major 4-hydroxy-3- nitrophenylacetyl-specific B cell populations whose BCR are comprised of the knockin VH17.2.25 (VHT)-encoded H chain and the λ1 or λ2 L chain. In this study, we show the QM system is useful to examine how BCR signals guide a subset of B cells to the marginal zone (MZ). Compared with the control C57BL/6 mice, the QM mice had ∼2.7-fold increased number of B cells exhibiting the MZ B cell phenotype and a larger MZ area in the spleen. Interestingly, VHT/λ2 B cells significantly predominated over VHT/λ1 B cells in MZ-(VHT/λ1:V HT/λ2 ≈ 3:7) and transitional 2-B cell subsets, while these two populations were comparable in immature, transitional 1, and mature counterparts. Thus, the biased use of λ2 in the MZ B cells may be the result of selection in the periphery. The enlargement of MZ B cell compartment and the preferred recruitment of the VHT/λ2 B cells were further augmented by doubling the VHT gene, but dampened by the dysfunction of Bruton's tyrosine kinase, suggesting a positive role of BCR signaling in this selection. Comparison of Ag specificity between V HT/λ1 and VHT/λ2 IgM mAbs revealed a polyreactive nature of the VHT/λ2 BCR, including the reactivity with ssDNA. Taken together, it is suggested that poly reactivity (including self-reactivity) of BCR is crucial in driving B cells to differentiate into the MZ phenotype.",
author = "Naoki Kanayama and Marilia Cascalho and Hitoshi Ohmori",
year = "2005",
month = "2",
day = "1",
language = "English",
volume = "174",
pages = "1438--1445",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "3",

}

TY - JOUR

T1 - Analysis of marginal zone B cell development in the mouse with limited B cell diversity

T2 - Role of the antigen receptor signals in the recruitment of B cells to the marginal zone

AU - Kanayama, Naoki

AU - Cascalho, Marilia

AU - Ohmori, Hitoshi

PY - 2005/2/1

Y1 - 2005/2/1

N2 - The quasimonoclonal (QM) mouse provides an intelligible model to analyze the B cell selection as the competition between two major 4-hydroxy-3- nitrophenylacetyl-specific B cell populations whose BCR are comprised of the knockin VH17.2.25 (VHT)-encoded H chain and the λ1 or λ2 L chain. In this study, we show the QM system is useful to examine how BCR signals guide a subset of B cells to the marginal zone (MZ). Compared with the control C57BL/6 mice, the QM mice had ∼2.7-fold increased number of B cells exhibiting the MZ B cell phenotype and a larger MZ area in the spleen. Interestingly, VHT/λ2 B cells significantly predominated over VHT/λ1 B cells in MZ-(VHT/λ1:V HT/λ2 ≈ 3:7) and transitional 2-B cell subsets, while these two populations were comparable in immature, transitional 1, and mature counterparts. Thus, the biased use of λ2 in the MZ B cells may be the result of selection in the periphery. The enlargement of MZ B cell compartment and the preferred recruitment of the VHT/λ2 B cells were further augmented by doubling the VHT gene, but dampened by the dysfunction of Bruton's tyrosine kinase, suggesting a positive role of BCR signaling in this selection. Comparison of Ag specificity between V HT/λ1 and VHT/λ2 IgM mAbs revealed a polyreactive nature of the VHT/λ2 BCR, including the reactivity with ssDNA. Taken together, it is suggested that poly reactivity (including self-reactivity) of BCR is crucial in driving B cells to differentiate into the MZ phenotype.

AB - The quasimonoclonal (QM) mouse provides an intelligible model to analyze the B cell selection as the competition between two major 4-hydroxy-3- nitrophenylacetyl-specific B cell populations whose BCR are comprised of the knockin VH17.2.25 (VHT)-encoded H chain and the λ1 or λ2 L chain. In this study, we show the QM system is useful to examine how BCR signals guide a subset of B cells to the marginal zone (MZ). Compared with the control C57BL/6 mice, the QM mice had ∼2.7-fold increased number of B cells exhibiting the MZ B cell phenotype and a larger MZ area in the spleen. Interestingly, VHT/λ2 B cells significantly predominated over VHT/λ1 B cells in MZ-(VHT/λ1:V HT/λ2 ≈ 3:7) and transitional 2-B cell subsets, while these two populations were comparable in immature, transitional 1, and mature counterparts. Thus, the biased use of λ2 in the MZ B cells may be the result of selection in the periphery. The enlargement of MZ B cell compartment and the preferred recruitment of the VHT/λ2 B cells were further augmented by doubling the VHT gene, but dampened by the dysfunction of Bruton's tyrosine kinase, suggesting a positive role of BCR signaling in this selection. Comparison of Ag specificity between V HT/λ1 and VHT/λ2 IgM mAbs revealed a polyreactive nature of the VHT/λ2 BCR, including the reactivity with ssDNA. Taken together, it is suggested that poly reactivity (including self-reactivity) of BCR is crucial in driving B cells to differentiate into the MZ phenotype.

UR - http://www.scopus.com/inward/record.url?scp=12444289439&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=12444289439&partnerID=8YFLogxK

M3 - Article

VL - 174

SP - 1438

EP - 1445

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 3

ER -