B cell-specific MHC class II deletion reveals multiple nonredundant roles for B cell antigen presentation in murine lupus

Josephine R. Giles, Michael Kashgarian, Pandelakis Koni, Mark J. Shlomchik

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

B cells have both Ab-dependent and Ab-independent functions in systemic autoimmune diseases, including systemic lupus erythematosus (SLE). Ab-independent functions are known to be important, because mice with B cells but no secreted Ig have severe disease. These functions could include roles in lymphoid development, cytokine secretion, and Ag presentation; however, these possibilities have not been directly tested in SLE models. In this study, we show by lineage-specific ablation of MHC class II (MHCII) that B cell Ag presentation plays a nonredundant role in CD4+ T cell activation and effector differentiation in the MRL.Faslpr mouse model of SLE. MHCII-mediated interactions between B and T cells further promote B cell proliferation and differentiation, and, in fact, inefficient MHCII deletion on B cells led to strong selection of escaped cells in activated and plasmablast compartments, further underscoring the central role of B cell Ag presentation. Despite the leakiness in the system, B cell-specific MHCII deletion resulted in substantially ameliorated clinical disease. Hence, B cell Ag presentation is critical for T and B cell activation and differentiation, as well as target organ damage.

Original languageEnglish (US)
Pages (from-to)2571-2579
Number of pages9
JournalJournal of Immunology
Volume195
Issue number6
DOIs
StatePublished - Sep 15 2015

Fingerprint

Antigen Presentation
B-Lymphocytes
Systemic Lupus Erythematosus
T-Lymphocytes
Cell Differentiation
Autoimmune Diseases
Cell Proliferation
Cytokines

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

B cell-specific MHC class II deletion reveals multiple nonredundant roles for B cell antigen presentation in murine lupus. / Giles, Josephine R.; Kashgarian, Michael; Koni, Pandelakis; Shlomchik, Mark J.

In: Journal of Immunology, Vol. 195, No. 6, 15.09.2015, p. 2571-2579.

Research output: Contribution to journalArticle

Giles, Josephine R. ; Kashgarian, Michael ; Koni, Pandelakis ; Shlomchik, Mark J. / B cell-specific MHC class II deletion reveals multiple nonredundant roles for B cell antigen presentation in murine lupus. In: Journal of Immunology. 2015 ; Vol. 195, No. 6. pp. 2571-2579.
@article{3545a91401d3486b81d5561ec162bda6,
title = "B cell-specific MHC class II deletion reveals multiple nonredundant roles for B cell antigen presentation in murine lupus",
abstract = "B cells have both Ab-dependent and Ab-independent functions in systemic autoimmune diseases, including systemic lupus erythematosus (SLE). Ab-independent functions are known to be important, because mice with B cells but no secreted Ig have severe disease. These functions could include roles in lymphoid development, cytokine secretion, and Ag presentation; however, these possibilities have not been directly tested in SLE models. In this study, we show by lineage-specific ablation of MHC class II (MHCII) that B cell Ag presentation plays a nonredundant role in CD4+ T cell activation and effector differentiation in the MRL.Faslpr mouse model of SLE. MHCII-mediated interactions between B and T cells further promote B cell proliferation and differentiation, and, in fact, inefficient MHCII deletion on B cells led to strong selection of escaped cells in activated and plasmablast compartments, further underscoring the central role of B cell Ag presentation. Despite the leakiness in the system, B cell-specific MHCII deletion resulted in substantially ameliorated clinical disease. Hence, B cell Ag presentation is critical for T and B cell activation and differentiation, as well as target organ damage.",
author = "Giles, {Josephine R.} and Michael Kashgarian and Pandelakis Koni and Shlomchik, {Mark J.}",
year = "2015",
month = "9",
day = "15",
doi = "10.4049/jimmunol.1500792",
language = "English (US)",
volume = "195",
pages = "2571--2579",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "6",

}

TY - JOUR

T1 - B cell-specific MHC class II deletion reveals multiple nonredundant roles for B cell antigen presentation in murine lupus

AU - Giles, Josephine R.

AU - Kashgarian, Michael

AU - Koni, Pandelakis

AU - Shlomchik, Mark J.

PY - 2015/9/15

Y1 - 2015/9/15

N2 - B cells have both Ab-dependent and Ab-independent functions in systemic autoimmune diseases, including systemic lupus erythematosus (SLE). Ab-independent functions are known to be important, because mice with B cells but no secreted Ig have severe disease. These functions could include roles in lymphoid development, cytokine secretion, and Ag presentation; however, these possibilities have not been directly tested in SLE models. In this study, we show by lineage-specific ablation of MHC class II (MHCII) that B cell Ag presentation plays a nonredundant role in CD4+ T cell activation and effector differentiation in the MRL.Faslpr mouse model of SLE. MHCII-mediated interactions between B and T cells further promote B cell proliferation and differentiation, and, in fact, inefficient MHCII deletion on B cells led to strong selection of escaped cells in activated and plasmablast compartments, further underscoring the central role of B cell Ag presentation. Despite the leakiness in the system, B cell-specific MHCII deletion resulted in substantially ameliorated clinical disease. Hence, B cell Ag presentation is critical for T and B cell activation and differentiation, as well as target organ damage.

AB - B cells have both Ab-dependent and Ab-independent functions in systemic autoimmune diseases, including systemic lupus erythematosus (SLE). Ab-independent functions are known to be important, because mice with B cells but no secreted Ig have severe disease. These functions could include roles in lymphoid development, cytokine secretion, and Ag presentation; however, these possibilities have not been directly tested in SLE models. In this study, we show by lineage-specific ablation of MHC class II (MHCII) that B cell Ag presentation plays a nonredundant role in CD4+ T cell activation and effector differentiation in the MRL.Faslpr mouse model of SLE. MHCII-mediated interactions between B and T cells further promote B cell proliferation and differentiation, and, in fact, inefficient MHCII deletion on B cells led to strong selection of escaped cells in activated and plasmablast compartments, further underscoring the central role of B cell Ag presentation. Despite the leakiness in the system, B cell-specific MHCII deletion resulted in substantially ameliorated clinical disease. Hence, B cell Ag presentation is critical for T and B cell activation and differentiation, as well as target organ damage.

UR - http://www.scopus.com/inward/record.url?scp=84941773482&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84941773482&partnerID=8YFLogxK

U2 - 10.4049/jimmunol.1500792

DO - 10.4049/jimmunol.1500792

M3 - Article

VL - 195

SP - 2571

EP - 2579

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 6

ER -