scholarly journals Control of the T Follicular Helper–Germinal Center B-Cell Axis by CD8 + Regulatory T Cells Limits Atherosclerosis and Tertiary Lymphoid Organ Development

Circulation ◽  
2015 ◽  
Vol 131 (6) ◽  
pp. 560-570 ◽  
Author(s):  
Marc Clement ◽  
Kevin Guedj ◽  
Francesco Andreata ◽  
Marion Morvan ◽  
Laetitia Bey ◽  
...  
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
B Cell ◽  
Germinal Center ◽  
Cell Function ◽  
Lymphoid Organs ◽  
Cell Axis ◽  
Follicular Helper ◽  
Germinal Center B Cell ◽  
Apolipoprotein E Knockout Mice

Background— The atheromodulating activity of B cells during the development of atherosclerosis is well documented, but the mechanisms by which these cells are regulated have not been investigated. Methods and Results— Here, we analyzed the contribution of Qa-1–restricted CD8 + regulatory T cells to the control of the T follicular helper–germinal center B-cell axis during atherogenesis. Genetic disruption of CD8 + regulatory T cell function in atherosclerosis-prone apolipoprotein E knockout mice resulted in overactivation of this axis in secondary lymphoid organs, led to the increased development of tertiary lymphoid organs in the aorta, and enhanced disease development. In contrast, restoring control of the T follicular helper–germinal center B-cell axis by blocking the ICOS-ICOSL pathway reduced the development of atherosclerosis and the formation of tertiary lymphoid organs. Moreover, analyses of human atherosclerotic aneurysmal arteries by flow cytometry, gene expression analysis, and immunofluorescence confirmed the presence of T follicular helper cells within tertiary lymphoid organs. Conclusions— This study is the first to demonstrate that the T follicular helper–germinal center B-cell axis is proatherogenic and that CD8 + regulatory T cells control the germinal center reaction in both secondary and tertiary lymphoid organs. Therefore, disrupting this axis represents an innovative therapeutic approach.

scholarly journals Germinal Center B Cell and T Follicular Helper Cell Development Initiates in the Interfollicular Zone

Immunity ◽  
2011 ◽  
Vol 34 (6) ◽  
pp. 947-960 ◽  
Author(s):  
Steven M. Kerfoot ◽  
Gur Yaari ◽  
Jaymin R. Patel ◽  
Kody L. Johnson ◽  
David G. Gonzalez ◽  
...  
Keyword(s):  
B Cell ◽  
Germinal Center ◽  
Cell Development ◽  
Helper Cell ◽  
Follicular Helper ◽  
Germinal Center B Cell ◽  
T Follicular Helper Cell

scholarly journals CD10 delineates a subset of human IL-4 producing follicular helper T cells involved in the survival of follicular lymphoma B cells

Blood ◽  
2015 ◽  
Vol 125 (15) ◽  
pp. 2381-2385 ◽  
Author(s):  
Patricia Amé-Thomas ◽  
Sylvia Hoeller ◽  
Catherine Artchounin ◽  
Jan Misiak ◽  
Mounia Sabrina Braza ◽  
...  
Keyword(s):  
T Cells ◽  
B Cells ◽  
Follicular Lymphoma ◽  
B Cell ◽  
Germinal Center ◽  
Helper T Cells ◽  
Follicular Helper T Cells ◽  
Follicular Helper ◽  
Key Points ◽  
Cell Niche

Key Points CD10 identifies a unique subset of fully functional germinal center TFH that are activated and amplified within the FL cell niche. FL CD10pos TFH specifically display an IL-4hiIFN-γlo cytokine profile and encompass the malignant B-cell-supportive TFH subset.

scholarly journals Defective inhibition of B-cell proliferation by Wiskott-Aldrich syndrome protein-deficient regulatory T cells

Blood ◽  
2011 ◽  
Vol 117 (24) ◽  
pp. 6608-6611 ◽  
Author(s):  
Marsilio Adriani ◽  
Krysten A. Jones ◽  
Toru Uchiyama ◽  
Martha R. Kirby ◽  
Christopher Silvin ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
T Cells ◽  
Regulatory T Cells ◽  
B Cell ◽  
Cell Function ◽  
Granzyme B ◽  
Suppressor Activity ◽  
Wiskott Aldrich Syndrome ◽  
Helper Function ◽  
Inherited Immunodeficiency

Abstract Wiskott-Aldrich syndrome (WAS) is an inherited immunodeficiency characterized by high incidence of autoantibody-mediated autoimmune complications. Such a feature has been associated with defective suppressor activity of WAS protein-deficient, naturally occurring CD4+CD25+Foxp3+ regulatory T cells on responder T cells. However, it remains to be established whether the altered B-cell tolerance reported in WAS patients and Was knockout (WKO) mice is secondary to abnormalities in the direct suppression of B-cell function by nTreg cells or to impaired regulation of T-helper function. Because activated nTreg cells are known to induce granzyme B–mediated B-cell killing, we decided to evaluate the regulatory capabilities of WKO nTregs on B lymphocytes. We found that preactivated WKO nTreg cells failed to effectively suppress B-cell proliferation and that such a defect was associated with reduced killing of B cells and significantly decreased degranulation of granzyme B. Altogether, these results provide additional mechanistic insights into the loss of immune tolerance in WAS.

scholarly journals Downregulation of FOXP1 is required during germinal center B-cell function

Blood ◽  
2013 ◽  
Vol 121 (21) ◽  
pp. 4311-4320 ◽  
Author(s):  
Ainara Sagardoy ◽  
Jose I. Martinez-Ferrandis ◽  
Sergio Roa ◽  
Karen L. Bunting ◽  
María Angela Aznar ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
B Cell ◽  
Germinal Center ◽  
Cell Function ◽  
Germinal Centers ◽  
B Cell Function ◽  
Germinal Center B Cell ◽  
Key Points ◽  
And Function

Key Points FOXP1 is downregulated in germinal centers, inversely to BCL6, whereby it regulates a network of genes, half of which are also BCL6 targets. In transgenic mice, constitutive FOXP1 expression impairs GC formation and function, which might contribute to B-cell lymphomagenesis.

scholarly journals Chronic CD70-Driven Costimulation Impairs IgG Responses by Instructing T Cells to Inhibit Germinal Center B Cell Formation through FasL-Fas Interactions

2009 ◽  
Vol 183 (10) ◽  
pp. 6442-6451 ◽  
Author(s):  
Cathrien R. L. Beishuizen ◽  
Natasja A. M. Kragten ◽  
Louis Boon ◽  
Martijn A. Nolte ◽  
Rene A. W. van Lier ◽  
...  
Keyword(s):  
T Cells ◽  
B Cell ◽  
Germinal Center ◽  
Cell Formation ◽  
Germinal Center B Cell

scholarly journals Reconstitution of T follicular helper-humoral immune axis with elimination of hepatitis C virus

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Arshi Khanam ◽  
Shyamasundaran Kottilil ◽  
Eleanor Wilson
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
B Cells ◽  
B Cell ◽  
Cell Function ◽  
Memory Cell ◽  
Hcv Rna ◽  
Regulatory B Cells ◽  
Cell Axis ◽  
Follicular Helper

AbstractExhaustion of Hepatitis C Virus (HCV)-specific T cells and abnormal B cell function is a hallmark of chronic HCV infection. Direct-acting antiviral (DAA) therapies are effective in achieving sustained virologic response (SVR), however, whether successful DAA treatment reconstitute T follicular helper (TFH)-B cell axis in HCV patients is unclear. Here, we aimed to evaluate the immunological changes in global and HCV-specific CD4 + CXCR5 + TFH, CD4 + CXCR5-T and B cells in 20 HCV patients who achieved SVR with Sofosbuvir and Ledipasvir for 12 weeks and compared with 15 healthy controls (HC). Global and HCV-specific CD4 + CXCR5 + TFH, CD4 + CXCR5-T and CD19 + B cells had significant phenotypic and functional reconstitution post DAA therapy. Reconstitution of effector, central and terminally differentiated memory cell population and increased ICOS and BCL6 expression was seen in HCV patients at SVR12. HCV-specific cytokines were also improved post DAA. Exhausted and regulatory B cells were declined whereas memory B cells were expanded post DAA therapy. Importantly, frequencies of TFH cells were significantly associated with HCV RNA reduction, expansion of memory B and plasmablasts, while negatively associated with exhausted/regulatory B cells. Our results demonstrate that SVR with DAA therapy is effective in the reconstitution of phenotypic and functional abnormalities of TFH-B cell axis.

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