IFN-γ receptor and STAT1 signaling in B cells are central to spontaneous germinal center formation and autoimmunity

Domeier, Phillip P; Chodisetti, Sathi Babu; Soni, Chetna; Schell, Stephanie L.; Elias, Melinda J.; Wong, Eric B.; Cooper, Timothy K.; Kitamura, Daisuke; Rahman, Ziaur S. M.

doi:10.1084/jem.20151722

Cited by 172 publications

(181 citation statements)

References 63 publications

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“…Others have previously reported different requirements for GC formation in spontaneous autoimmunity versus deliberate immunization, with IFN-γR needed for the former but not the latter event (30,31). These observations, together with another observation that TLR7 expression in B cells is needed for GC appearance in spontaneous autoimmunity (39), are in line with our findings with respect to T-bet + ABCs, since ABC formation depends on IFN-γ and TLR7 signaling in B cells (11).…”

Section: Discussionsupporting

confidence: 92%

“…These observations, together with another observation that TLR7 expression in B cells is needed for GC appearance in spontaneous autoimmunity (39), are in line with our findings with respect to T-bet + ABCs, since ABC formation depends on IFN-γ and TLR7 signaling in B cells (11). However, the results of some others differ from those reported here in one respect, since some, but not all other studies found that T-bet expression in B cells was not required for spontaneous GC formation (30,31).…”

Section: Discussionsupporting

confidence: 91%

“…These findings are in line with recent reports indicating that IFN-γR expression in B cells is required for the formation of spontaneous GCs during autoimmunity (30,31) and indicate differential requirements for spontaneous and deliberate GC formation. This finding should be further examined in the future.…”

Section: 8supporting

confidence: 92%

See 2 more Smart Citations

B cells expressing the transcription factor T-bet drive lupus-like autoimmunity

Rubtsova¹,

Rubtsov²,

Thurman³

et al. 2017

Journal of Clinical Investigation

225

283

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Section: Discussionsupporting

confidence: 92%

Section: Discussionsupporting

confidence: 91%

See 1 more Smart Citation

B cells expressing the transcription factor T-bet drive lupus-like autoimmunity

Rubtsova¹,

Rubtsov²,

Thurman³

et al. 2017

Journal of Clinical Investigation

225

283

View full text Add to dashboard Cite

“…Spontaneous germinal centre (GC) responses that are associated with autoantibody production are implicated in the pathogenesis of SLE. The pathways through which GC B cell tolerance break down are not clear, but in mouse models it was recently shown that IFN-γR signaling in B cells as well as B cell IFN-γ production were critical initial steps for spontaneous GC development leading to autoimmunity6162. Interestingly, SLE patients also display increased BAFF serum levels that correlate with disease activity63.…”

Section: Discussionmentioning

confidence: 99%

IFN type I and II induce BAFF secretion from human decidual stromal cells

Lundell

Nordström

Andersson

et al. 2017

Sci Rep

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B cell activating factor (BAFF) is a critical cytokine for maturation of immature B cells. In murine lymph nodes, BAFF is mainly produced by podoplanin-expressing stromal cells. We have previously shown that circulating BAFF levels are maximal at birth, and that farmers’ children exhibit higher BAFF levels in cord blood than non-farmers’ children. Here, we sought to investigate whether maternal-derived decidual stromal cells from placenta secrete BAFF and examine what factors could stimulate this production. We found that podoplanin is expressed in decidua basalis and in the underlying villous tissue as well as on isolated maternal-derived decidual stromal cells. Decidual stromal cells produced BAFF when stimulated with IFN-γ and IFN-α, and NK cells and NK-T-like cells competent of IFN-γ production were isolated from the decidua. Finally, B cells at different maturational stages are present in decidua and all expressed BAFF-R, while stromal cells did not. These findings suggest that decidual stromal cells are a cellular source of BAFF for B cells present in decidua during pregnancy.

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“…Moncef Zouali 1,2 and Gregory Tsay 3,4 Rahman′s data also indicate a critical B cell-intrinsic role of interferon γ receptor (IFNγR) signaling in accentuating Spt-GCs and autoimmune responses in B6.Sle1b mice (4). They suggest that IFNγR and STAT1 signaling control Spt-GC and Tfh formation by driving T-bet expression and IFNγ production by B cells.…”

Section: Developing Connections Among B Lymphocytes and Deregulated Pmentioning

confidence: 95%

Developing Connections among B Lymphocytes and Deregulated Pathways in Autoimmunity

Zouali

Tsay

2016

Mol Med

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Immunologists have long investigated B lymphocytes as solely antibody-producing cells. With further studies, it became clear that B cells can exert a variety of functions within the immune system and beyond. As a result, B cells are considered promising targets for immunotherapy in a variety of disorders. Recently, experts in B cell biology and autoimmunity convened to discuss important stepping stones to decipher the complexity of B lymphocyte-mediated pathways in autoimmune diseases. Twenty-five years ago, the first report describing the clinical efficacy of depleting B lymphocytes in autoimmune diseases was published (1). This also marked organization of the first International Conference on B Cells and Autoimmunity, held in 2001 in Bergen, Norway. Since then, the credentials of B cells as essential players in autoimmune disease have been well established. For its sixth edition, this conference series settled along the shores of Sun Moon Lake in the heart of Taiwan on August 16-18, 2016, to view and discuss recent advances in different facets of B cell biology and put them in the perspective of understanding autoimmunity and designing effective immunointervention strategies. Following the tradition established in 2001, the conference was a forum where basic immunologists and their clinically trained colleagues met to discuss hot topics of autoimmunity research. Speakers from four continents discussed some of their new data and insights and brought considerable excitement to the conference in the refreshingly beautiful and elegant landscape of Sun Moon Lake and its indescribable charm. B L Y M P H O C Y T E S A N D A U T O I M M U N I T Y

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IFN-γ receptor and STAT1 signaling in B cells are central to spontaneous germinal center formation and autoimmunity

Abstract: B cell–intrinsic IFN-γ receptor signaling through STAT1 is required for the generation of spontaneous germinal centers, which can lead to pathogenic autoantibody production.

Cited by 172 publications

References 63 publications

B cells expressing the transcription factor T-bet drive lupus-like autoimmunity

B cells expressing the transcription factor T-bet drive lupus-like autoimmunity

IFN type I and II induce BAFF secretion from human decidual stromal cells

Developing Connections among B Lymphocytes and Deregulated Pathways in Autoimmunity

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