Regulation of B cell tolerance by the lupus susceptibility gene Ly108

Kirthi Raman Kumar, Liunan Li, Mei Yan, Madhavi Bhaskarabhatla, Angela B. Mobley, Charles Nguyen, Jill M. Mooney, John D. Schatzle, Edward K. Wakeland, Chandra Mohan

Research output: Contribution to journalArticle

190 Citations (Scopus)

Abstract

The susceptibility locus for the autoimmune disease lupus on murine chromosome 1, Sle1z/Sle1bz, and the orthologous human locus are associated with production of autoantibody to chromatin. We report that the presence of Sle1z/Sle1bz impairs B cell anergy, receptor revision, and deletion. Members of the SLAM costimulatory molecule family constitute prime candidates for Sle1bz, among which the Ly108.1 isoform of the Ly108 gene was most highly expressed in immature B cells from lupus-prone B6.Sle1z mice. The normal Ly108.2 allele, but not the lupus-associated Ly108.1 allele, was found to sensitize immature B cells to deletion and RAG reexpression. As a potential regulator of tolerance checkpoints, Ly108 may censor self-reactive B cells, hence safeguarding against autoimmunity.

Original languageEnglish (US)
Pages (from-to)1665-1669
Number of pages5
JournalScience
Volume312
Issue number5780
DOIs
StatePublished - Jun 16 2006

Fingerprint

B-Lymphoid Precursor Cells
B-Lymphocytes
Alleles
Chromosomes, Human, Pair 1
Autoimmunity
Autoantibodies
Genes
Autoimmune Diseases
Chromatin
Protein Isoforms

ASJC Scopus subject areas

  • General

Cite this

Kumar, K. R., Li, L., Yan, M., Bhaskarabhatla, M., Mobley, A. B., Nguyen, C., ... Mohan, C. (2006). Regulation of B cell tolerance by the lupus susceptibility gene Ly108. Science, 312(5780), 1665-1669. https://doi.org/10.1126/science.1125893

Regulation of B cell tolerance by the lupus susceptibility gene Ly108. / Kumar, Kirthi Raman; Li, Liunan; Yan, Mei; Bhaskarabhatla, Madhavi; Mobley, Angela B.; Nguyen, Charles; Mooney, Jill M.; Schatzle, John D.; Wakeland, Edward K.; Mohan, Chandra.

In: Science, Vol. 312, No. 5780, 16.06.2006, p. 1665-1669.

Research output: Contribution to journalArticle

Kumar, KR, Li, L, Yan, M, Bhaskarabhatla, M, Mobley, AB, Nguyen, C, Mooney, JM, Schatzle, JD, Wakeland, EK & Mohan, C 2006, 'Regulation of B cell tolerance by the lupus susceptibility gene Ly108', Science, vol. 312, no. 5780, pp. 1665-1669. https://doi.org/10.1126/science.1125893
Kumar KR, Li L, Yan M, Bhaskarabhatla M, Mobley AB, Nguyen C et al. Regulation of B cell tolerance by the lupus susceptibility gene Ly108. Science. 2006 Jun 16;312(5780):1665-1669. https://doi.org/10.1126/science.1125893
Kumar, Kirthi Raman ; Li, Liunan ; Yan, Mei ; Bhaskarabhatla, Madhavi ; Mobley, Angela B. ; Nguyen, Charles ; Mooney, Jill M. ; Schatzle, John D. ; Wakeland, Edward K. ; Mohan, Chandra. / Regulation of B cell tolerance by the lupus susceptibility gene Ly108. In: Science. 2006 ; Vol. 312, No. 5780. pp. 1665-1669.
@article{93889e5f488842dd8357e52915051dda,
title = "Regulation of B cell tolerance by the lupus susceptibility gene Ly108",
abstract = "The susceptibility locus for the autoimmune disease lupus on murine chromosome 1, Sle1z/Sle1bz, and the orthologous human locus are associated with production of autoantibody to chromatin. We report that the presence of Sle1z/Sle1bz impairs B cell anergy, receptor revision, and deletion. Members of the SLAM costimulatory molecule family constitute prime candidates for Sle1bz, among which the Ly108.1 isoform of the Ly108 gene was most highly expressed in immature B cells from lupus-prone B6.Sle1z mice. The normal Ly108.2 allele, but not the lupus-associated Ly108.1 allele, was found to sensitize immature B cells to deletion and RAG reexpression. As a potential regulator of tolerance checkpoints, Ly108 may censor self-reactive B cells, hence safeguarding against autoimmunity.",
author = "Kumar, {Kirthi Raman} and Liunan Li and Mei Yan and Madhavi Bhaskarabhatla and Mobley, {Angela B.} and Charles Nguyen and Mooney, {Jill M.} and Schatzle, {John D.} and Wakeland, {Edward K.} and Chandra Mohan",
year = "2006",
month = "6",
day = "16",
doi = "10.1126/science.1125893",
language = "English (US)",
volume = "312",
pages = "1665--1669",
journal = "Science",
issn = "0036-8075",
publisher = "American Association for the Advancement of Science",
number = "5780",

}

TY - JOUR

T1 - Regulation of B cell tolerance by the lupus susceptibility gene Ly108

AU - Kumar, Kirthi Raman

AU - Li, Liunan

AU - Yan, Mei

AU - Bhaskarabhatla, Madhavi

AU - Mobley, Angela B.

AU - Nguyen, Charles

AU - Mooney, Jill M.

AU - Schatzle, John D.

AU - Wakeland, Edward K.

AU - Mohan, Chandra

PY - 2006/6/16

Y1 - 2006/6/16

N2 - The susceptibility locus for the autoimmune disease lupus on murine chromosome 1, Sle1z/Sle1bz, and the orthologous human locus are associated with production of autoantibody to chromatin. We report that the presence of Sle1z/Sle1bz impairs B cell anergy, receptor revision, and deletion. Members of the SLAM costimulatory molecule family constitute prime candidates for Sle1bz, among which the Ly108.1 isoform of the Ly108 gene was most highly expressed in immature B cells from lupus-prone B6.Sle1z mice. The normal Ly108.2 allele, but not the lupus-associated Ly108.1 allele, was found to sensitize immature B cells to deletion and RAG reexpression. As a potential regulator of tolerance checkpoints, Ly108 may censor self-reactive B cells, hence safeguarding against autoimmunity.

AB - The susceptibility locus for the autoimmune disease lupus on murine chromosome 1, Sle1z/Sle1bz, and the orthologous human locus are associated with production of autoantibody to chromatin. We report that the presence of Sle1z/Sle1bz impairs B cell anergy, receptor revision, and deletion. Members of the SLAM costimulatory molecule family constitute prime candidates for Sle1bz, among which the Ly108.1 isoform of the Ly108 gene was most highly expressed in immature B cells from lupus-prone B6.Sle1z mice. The normal Ly108.2 allele, but not the lupus-associated Ly108.1 allele, was found to sensitize immature B cells to deletion and RAG reexpression. As a potential regulator of tolerance checkpoints, Ly108 may censor self-reactive B cells, hence safeguarding against autoimmunity.

UR - http://www.scopus.com/inward/record.url?scp=33745161013&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33745161013&partnerID=8YFLogxK

U2 - 10.1126/science.1125893

DO - 10.1126/science.1125893

M3 - Article

VL - 312

SP - 1665

EP - 1669

JO - Science

JF - Science

SN - 0036-8075

IS - 5780

ER -