Antigen receptor editing in anti-DNA transitional B cells deficient for surface IgM

Kerstin Kiefer, Pamela B. Nakajima, Jennifer Oshinsky, Steven H. Seeholzer, Marko Radic, Gayle C. Bosma, Melvin J. Bosma

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

In response to encounter with self-Ag, autoreactive B cells may undergo secondary L chain gene rearrangement (receptor editing) and change the specificity of their Ag receptor. Knowing at what differentiative stage(s) developing B cells undergo receptor editing is important for understanding how self-reactive B cells are regulated. In this study, in mice with Ig transgenes coding for anti-self (DNA) Ab, we report dsDNA breaks indicative of ongoing secondary L chain rearrangement not only in bone marrow cells with a pre-B/B cell phenotype but also in immature/transitional splenic B cells with little or no surface IgM (sIgM-/low). L chain-edited transgenic B cells were detectable in spleen but not bone marrow and were still found to produce Ab specific for DNA (and apoptotic cells), albeit with lower affinity for DNA than the unedited transgenic Ab. We conclude that L chain editing in anti-DNA-transgenic B cells is not only ongoing in bone marrow but also in spleen. Indeed, transfer of sIgM-/low anti-DNA splenic B cells into SCID mice resulted in the appearance of a L chain editor (Vλx) in the serum of engrafted recipients. Finally, we also report evidence for ongoing L chain editing in sIgMlow transitional splenic B cells of wild-type mice.

Original languageEnglish (US)
Pages (from-to)6094-6106
Number of pages13
JournalJournal of Immunology
Volume180
Issue number9
DOIs
StatePublished - May 1 2008

Fingerprint

Antigen Receptors
B-Lymphoid Precursor Cells
Immunoglobulin M
B-Lymphocytes
DNA
Spleen
Bone Marrow
SCID Mice
Gene Rearrangement
Transgenes
Bone Marrow Cells
Phenotype
Serum

All Science Journal Classification (ASJC) codes

  • Immunology

Cite this

Kiefer, K., Nakajima, P. B., Oshinsky, J., Seeholzer, S. H., Radic, M., Bosma, G. C., & Bosma, M. J. (2008). Antigen receptor editing in anti-DNA transitional B cells deficient for surface IgM. Journal of Immunology, 180(9), 6094-6106. https://doi.org/10.4049/jimmunol.180.9.6094

Antigen receptor editing in anti-DNA transitional B cells deficient for surface IgM. / Kiefer, Kerstin; Nakajima, Pamela B.; Oshinsky, Jennifer; Seeholzer, Steven H.; Radic, Marko; Bosma, Gayle C.; Bosma, Melvin J.

In: Journal of Immunology, Vol. 180, No. 9, 01.05.2008, p. 6094-6106.

Research output: Contribution to journalArticle

Kiefer, K, Nakajima, PB, Oshinsky, J, Seeholzer, SH, Radic, M, Bosma, GC & Bosma, MJ 2008, 'Antigen receptor editing in anti-DNA transitional B cells deficient for surface IgM', Journal of Immunology, vol. 180, no. 9, pp. 6094-6106. https://doi.org/10.4049/jimmunol.180.9.6094
Kiefer, Kerstin ; Nakajima, Pamela B. ; Oshinsky, Jennifer ; Seeholzer, Steven H. ; Radic, Marko ; Bosma, Gayle C. ; Bosma, Melvin J. / Antigen receptor editing in anti-DNA transitional B cells deficient for surface IgM. In: Journal of Immunology. 2008 ; Vol. 180, No. 9. pp. 6094-6106.
@article{db1aa20dab4d4e99934431ded7004811,
title = "Antigen receptor editing in anti-DNA transitional B cells deficient for surface IgM",
abstract = "In response to encounter with self-Ag, autoreactive B cells may undergo secondary L chain gene rearrangement (receptor editing) and change the specificity of their Ag receptor. Knowing at what differentiative stage(s) developing B cells undergo receptor editing is important for understanding how self-reactive B cells are regulated. In this study, in mice with Ig transgenes coding for anti-self (DNA) Ab, we report dsDNA breaks indicative of ongoing secondary L chain rearrangement not only in bone marrow cells with a pre-B/B cell phenotype but also in immature/transitional splenic B cells with little or no surface IgM (sIgM-/low). L chain-edited transgenic B cells were detectable in spleen but not bone marrow and were still found to produce Ab specific for DNA (and apoptotic cells), albeit with lower affinity for DNA than the unedited transgenic Ab. We conclude that L chain editing in anti-DNA-transgenic B cells is not only ongoing in bone marrow but also in spleen. Indeed, transfer of sIgM-/low anti-DNA splenic B cells into SCID mice resulted in the appearance of a L chain editor (Vλx) in the serum of engrafted recipients. Finally, we also report evidence for ongoing L chain editing in sIgMlow transitional splenic B cells of wild-type mice.",
author = "Kerstin Kiefer and Nakajima, {Pamela B.} and Jennifer Oshinsky and Seeholzer, {Steven H.} and Marko Radic and Bosma, {Gayle C.} and Bosma, {Melvin J.}",
year = "2008",
month = "5",
day = "1",
doi = "10.4049/jimmunol.180.9.6094",
language = "English (US)",
volume = "180",
pages = "6094--6106",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "9",

}

TY - JOUR

T1 - Antigen receptor editing in anti-DNA transitional B cells deficient for surface IgM

AU - Kiefer, Kerstin

AU - Nakajima, Pamela B.

AU - Oshinsky, Jennifer

AU - Seeholzer, Steven H.

AU - Radic, Marko

AU - Bosma, Gayle C.

AU - Bosma, Melvin J.

PY - 2008/5/1

Y1 - 2008/5/1

N2 - In response to encounter with self-Ag, autoreactive B cells may undergo secondary L chain gene rearrangement (receptor editing) and change the specificity of their Ag receptor. Knowing at what differentiative stage(s) developing B cells undergo receptor editing is important for understanding how self-reactive B cells are regulated. In this study, in mice with Ig transgenes coding for anti-self (DNA) Ab, we report dsDNA breaks indicative of ongoing secondary L chain rearrangement not only in bone marrow cells with a pre-B/B cell phenotype but also in immature/transitional splenic B cells with little or no surface IgM (sIgM-/low). L chain-edited transgenic B cells were detectable in spleen but not bone marrow and were still found to produce Ab specific for DNA (and apoptotic cells), albeit with lower affinity for DNA than the unedited transgenic Ab. We conclude that L chain editing in anti-DNA-transgenic B cells is not only ongoing in bone marrow but also in spleen. Indeed, transfer of sIgM-/low anti-DNA splenic B cells into SCID mice resulted in the appearance of a L chain editor (Vλx) in the serum of engrafted recipients. Finally, we also report evidence for ongoing L chain editing in sIgMlow transitional splenic B cells of wild-type mice.

AB - In response to encounter with self-Ag, autoreactive B cells may undergo secondary L chain gene rearrangement (receptor editing) and change the specificity of their Ag receptor. Knowing at what differentiative stage(s) developing B cells undergo receptor editing is important for understanding how self-reactive B cells are regulated. In this study, in mice with Ig transgenes coding for anti-self (DNA) Ab, we report dsDNA breaks indicative of ongoing secondary L chain rearrangement not only in bone marrow cells with a pre-B/B cell phenotype but also in immature/transitional splenic B cells with little or no surface IgM (sIgM-/low). L chain-edited transgenic B cells were detectable in spleen but not bone marrow and were still found to produce Ab specific for DNA (and apoptotic cells), albeit with lower affinity for DNA than the unedited transgenic Ab. We conclude that L chain editing in anti-DNA-transgenic B cells is not only ongoing in bone marrow but also in spleen. Indeed, transfer of sIgM-/low anti-DNA splenic B cells into SCID mice resulted in the appearance of a L chain editor (Vλx) in the serum of engrafted recipients. Finally, we also report evidence for ongoing L chain editing in sIgMlow transitional splenic B cells of wild-type mice.

UR - http://www.scopus.com/inward/record.url?scp=44449154414&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=44449154414&partnerID=8YFLogxK

U2 - 10.4049/jimmunol.180.9.6094

DO - 10.4049/jimmunol.180.9.6094

M3 - Article

C2 - 18424731

AN - SCOPUS:44449154414

VL - 180

SP - 6094

EP - 6106

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 9

ER -