T Cell-Independent and Toll-like Receptor-Dependent Antigen-Driven Activation of Autoreactive B Cells

Robin A. Herlands; Sean R. Christensen; Rebecca A. Sweet; Uri Hershberg; Mark J. Shlomchik

doi:10.1016/j.immuni.2008.06.009

T Cell-Independent and Toll-like Receptor-Dependent Antigen-Driven Activation of Autoreactive B Cells

Robin A. Herlands, Sean R. Christensen, Rebecca A. Sweet, Uri Hershberg, Mark J. Shlomchik

Research output: Contribution to journal › Article › peer-review

Abstract

On the lupus-prone MRL-lpr/lpr (MRL-lpr) background, AM14 rheumatoid factor (RF) B cells are activated, differentiate into plasmablasts, and undergo somatic hypermutation outside of follicles. Using multiple strategies to impair T cells, we found that such AM14 B cell activation did not require T cells but could be modulated by them. In vitro, the signaling adaptor MyD88 is required for IgG anti-chromatin to stimulate AM14 B cell proliferation when T cells are absent. However, the roles of Toll-like receptors (TLRs) in AM14 B cell activation in vivo have not been investigated. We found that activation, expansion, and differentiation of AM14 B cells depended on MyD88; however, mice lacking either TLR7 or TLR9 displayed partial defects, indicating complex roles for these receptors. T cell-independent activation of certain autoreactive B cells, which gain stimuli via endogenous TLR ligands instead of T cells, may be the initial step in the generation of canonical autoantibodies.

Original language	English
Pages (from-to)	249-260
Number of pages	12
Journal	Immunity
Volume	29
Issue number	2
DOIs	https://doi.org/10.1016/j.immuni.2008.06.009
State	Published - 15 Aug 2008
Externally published	Yes

Bibliographical note

Funding Information:
We thank J. Craft and Z. Yin for generously providing the Tcrb −/− mice and UC-7 Ab. We thank M. Horniak, T. Hunt, M. Baez, and D. Kent for outstanding animal husbandry. We thank the members of the Shlomchik lab autoimmunity group for many useful discussions and A. Rothstein and J. Craft for critical comments on the manuscript. The research was supported by NIH grants P01-AI36529 and P01-AR050256.

Keywords

CELLIMMUNO
MOLIMMUNO

ASJC Scopus subject areas

Immunology and Allergy
Immunology
Infectious Diseases

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1016/j.immuni.2008.06.009

Cite this

@article{17b2b2bb1914498d99260e5c65d7d169,

title = "T Cell-Independent and Toll-like Receptor-Dependent Antigen-Driven Activation of Autoreactive B Cells",

abstract = "On the lupus-prone MRL-lpr/lpr (MRL-lpr) background, AM14 rheumatoid factor (RF) B cells are activated, differentiate into plasmablasts, and undergo somatic hypermutation outside of follicles. Using multiple strategies to impair T cells, we found that such AM14 B cell activation did not require T cells but could be modulated by them. In vitro, the signaling adaptor MyD88 is required for IgG anti-chromatin to stimulate AM14 B cell proliferation when T cells are absent. However, the roles of Toll-like receptors (TLRs) in AM14 B cell activation in vivo have not been investigated. We found that activation, expansion, and differentiation of AM14 B cells depended on MyD88; however, mice lacking either TLR7 or TLR9 displayed partial defects, indicating complex roles for these receptors. T cell-independent activation of certain autoreactive B cells, which gain stimuli via endogenous TLR ligands instead of T cells, may be the initial step in the generation of canonical autoantibodies.",

keywords = "CELLIMMUNO, MOLIMMUNO",

author = "Herlands, {Robin A.} and Christensen, {Sean R.} and Sweet, {Rebecca A.} and Uri Hershberg and Shlomchik, {Mark J.}",

note = "Funding Information: We thank J. Craft and Z. Yin for generously providing the Tcrb −/− mice and UC-7 Ab. We thank M. Horniak, T. Hunt, M. Baez, and D. Kent for outstanding animal husbandry. We thank the members of the Shlomchik lab autoimmunity group for many useful discussions and A. Rothstein and J. Craft for critical comments on the manuscript. The research was supported by NIH grants P01-AI36529 and P01-AR050256. ",

year = "2008",

month = aug,

day = "15",

doi = "10.1016/j.immuni.2008.06.009",

language = "English",

volume = "29",

pages = "249--260",

journal = "Immunity",

issn = "1074-7613",

publisher = "Cell Press",

number = "2",

}

TY - JOUR

T1 - T Cell-Independent and Toll-like Receptor-Dependent Antigen-Driven Activation of Autoreactive B Cells

AU - Herlands, Robin A.

AU - Christensen, Sean R.

AU - Sweet, Rebecca A.

AU - Hershberg, Uri

AU - Shlomchik, Mark J.

N1 - Funding Information: We thank J. Craft and Z. Yin for generously providing the Tcrb −/− mice and UC-7 Ab. We thank M. Horniak, T. Hunt, M. Baez, and D. Kent for outstanding animal husbandry. We thank the members of the Shlomchik lab autoimmunity group for many useful discussions and A. Rothstein and J. Craft for critical comments on the manuscript. The research was supported by NIH grants P01-AI36529 and P01-AR050256.

PY - 2008/8/15

Y1 - 2008/8/15

N2 - On the lupus-prone MRL-lpr/lpr (MRL-lpr) background, AM14 rheumatoid factor (RF) B cells are activated, differentiate into plasmablasts, and undergo somatic hypermutation outside of follicles. Using multiple strategies to impair T cells, we found that such AM14 B cell activation did not require T cells but could be modulated by them. In vitro, the signaling adaptor MyD88 is required for IgG anti-chromatin to stimulate AM14 B cell proliferation when T cells are absent. However, the roles of Toll-like receptors (TLRs) in AM14 B cell activation in vivo have not been investigated. We found that activation, expansion, and differentiation of AM14 B cells depended on MyD88; however, mice lacking either TLR7 or TLR9 displayed partial defects, indicating complex roles for these receptors. T cell-independent activation of certain autoreactive B cells, which gain stimuli via endogenous TLR ligands instead of T cells, may be the initial step in the generation of canonical autoantibodies.

AB - On the lupus-prone MRL-lpr/lpr (MRL-lpr) background, AM14 rheumatoid factor (RF) B cells are activated, differentiate into plasmablasts, and undergo somatic hypermutation outside of follicles. Using multiple strategies to impair T cells, we found that such AM14 B cell activation did not require T cells but could be modulated by them. In vitro, the signaling adaptor MyD88 is required for IgG anti-chromatin to stimulate AM14 B cell proliferation when T cells are absent. However, the roles of Toll-like receptors (TLRs) in AM14 B cell activation in vivo have not been investigated. We found that activation, expansion, and differentiation of AM14 B cells depended on MyD88; however, mice lacking either TLR7 or TLR9 displayed partial defects, indicating complex roles for these receptors. T cell-independent activation of certain autoreactive B cells, which gain stimuli via endogenous TLR ligands instead of T cells, may be the initial step in the generation of canonical autoantibodies.

KW - CELLIMMUNO

KW - MOLIMMUNO

UR - http://www.scopus.com/inward/record.url?scp=48749085121&partnerID=8YFLogxK

U2 - 10.1016/j.immuni.2008.06.009

DO - 10.1016/j.immuni.2008.06.009

M3 - Article

C2 - 18691914

AN - SCOPUS:48749085121

SN - 1074-7613

VL - 29

SP - 249

EP - 260

JO - Immunity

JF - Immunity

IS - 2

ER -

T Cell-Independent and Toll-like Receptor-Dependent Antigen-Driven Activation of Autoreactive B Cells

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this