scholarly journals CD8 Follicular T Cells Promote B Cell Antibody Class Switch in Autoimmune Disease

2018 ◽  
Vol 201 (1) ◽  
pp. 31-40 ◽  
Author(s):  
Kristen M. Valentine ◽  
Dan Davini ◽  
Travis J. Lawrence ◽  
Genevieve N. Mullins ◽  
Miguel Manansala ◽  
...  
Keyword(s):  
T Cells ◽  
Autoimmune Disease ◽  
B Cell ◽  
Class Switch ◽  
Cell Antibody ◽  
Antibody Class

scholarly journals B cell–derived IL-27 promotes control of persistent LCMV infection

2022 ◽  
Vol 119 (3) ◽  
pp. e2116741119
Author(s):  
Isaraphorn Pratumchai ◽  
Jaroslav Zak ◽  
Zhe Huang ◽  
Booki Min ◽  
Michael B. A. Oldstone ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cells ◽  
B Cell ◽  
Conditional Knockout ◽  
Cd4 T Cell ◽  
Viral Control ◽  
Class Switch ◽  
Antibody Class ◽  
Lcmv Infection

Recent studies have identified a critical role for B cell–produced cytokines in regulating both humoral and cellular immunity. Here, we show that B cells are an essential source of interleukin-27 (IL-27) during persistent lymphocytic choriomeningitis virus (LCMV) clone 13 (Cl-13) infection. By using conditional knockout mouse models with specific IL-27p28 deletion in B cells, we observed that B cell–derived IL-27 promotes survival of virus-specific CD4 T cells and supports functions of T follicular helper (Tfh) cells. Mechanistically, B cell–derived IL-27 promotes CD4 T cell function, antibody class switch, and the ability to control persistent LCMV infection. Deletion of IL-27ra in T cells demonstrated that T cell–intrinsic IL-27R signaling is essential for viral control, optimal CD4 T cell responses, and antibody class switch during persistent LCMV infection. Collectively, our findings identify a cellular mechanism whereby B cell–derived IL-27 drives antiviral immunity and antibody responses through IL-27 signaling on T cells to promote control of LCMV Cl-13 infection.

scholarly journals Follicular T cells are clonally and transcriptionally distinct in B cell-driven mouse autoimmune disease

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Elliot H. Akama-Garren ◽  
Theo van den Broek ◽  
Lea Simoni ◽  
Carlos Castrillon ◽  
Cees E. van der Poel ◽  
...  
Keyword(s):  
T Cells ◽  
Autoimmune Disease ◽  
B Cell ◽  
Single Cell ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Germinal Centers ◽  
Learning Approaches ◽  
Differential Gene ◽  
Disease Antigen

AbstractPathogenic autoantibodies contribute to tissue damage and clinical decline in autoimmune disease. Follicular T cells are central regulators of germinal centers, although their contribution to autoantibody-mediated disease remains unclear. Here we perform single cell RNA and T cell receptor (TCR) sequencing of follicular T cells in a mouse model of autoantibody-mediated disease, allowing for analyses of paired transcriptomes and unbiased TCRαβ repertoires at single cell resolution. A minority of clonotypes are preferentially shared amongst autoimmune follicular T cells and clonotypic expansion is associated with differential gene signatures in autoimmune disease. Antigen prediction using algorithmic and machine learning approaches indicates convergence towards shared specificities between non-autoimmune and autoimmune follicular T cells. However, differential autoimmune transcriptional signatures are preserved even amongst follicular T cells with shared predicted specificities. These results demonstrate that follicular T cells are phenotypically distinct in B cell-driven autoimmune disease, providing potential therapeutic targets to modulate autoantibody development.

scholarly journals How the Signaling Crosstalk of B Cell Receptor (BCR) and Co-Receptors Regulates Antibody Class Switch Recombination: A New Perspective of Checkpoints of BCR Signaling

2021 ◽  
Vol 12 ◽  
Author(s):  
Zhangguo Chen ◽  
Jing H. Wang
Keyword(s):  
B Cells ◽  
Immune Responses ◽  
B Cell ◽  
Dna Recombination ◽  
Class Switch Recombination ◽  
Cell Receptor ◽  
Signaling Crosstalk ◽  
Class Switch ◽  
Antibody Class ◽  
New Perspective

Mature B cells express B cell antigen receptor (BCR), toll-like receptors (TLR) and TNF family receptors including CD40 and B-cell activating factor receptor (BAFFR). These receptors transduce cellular signals to govern the physiological and pathological processes in B cells including B cell development and differentiation, survival, proliferation, and antibody-mediated immune responses as well as autoimmune diseases and B cell lymphomagenesis. Effective antibody-mediated immune responses require class switch recombination (CSR), a somatic DNA recombination event occurring at the immunoglobulin heavy chain (Igh) gene locus. Mature B cells initially express IgM as their BCR, and CSR enables the B cells to switch from expressing IgM to expressing different classes of antibodies including IgG, IgA or IgE that exhibit distinct effector functions. Here, we briefly review recent findings about how the signaling crosstalk of the BCR with TLRs, CD40 and BAFFR regulates CSR, antibody-mediate immune responses, and B cell anergy.

Follicular T Cells are Clonally and Transcriptionally Distinct in B Cell-Driven Autoimmune Disease

2020 ◽  
Author(s):  
Elliot Akama-Garren ◽  
Theo van den Broek ◽  
Lea Simoni ◽  
Carlos Castrillon ◽  
Cees van der Poel ◽  
...  
Keyword(s):  
T Cells ◽  
Autoimmune Disease ◽  
B Cell

scholarly journals Engineered FVIII-expressing cytotoxic T cells target and kill FVIII-specific B cells in vitro and in vivo

2018 ◽  
Vol 2 (18) ◽  
pp. 2332-2340 ◽  
Author(s):  
Kalpana Parvathaneni ◽  
David W. Scott
Keyword(s):  
T Cells ◽  
B Cells ◽  
B Cell ◽  
Cd8 T Cells ◽  
Hemophilia A ◽  
Cytotoxic T Cells ◽  
Cell Antibody ◽  
Engineered T Cells

Abstract Hemophilia A is an X-linked bleeding disorder caused by mutations in the factor VIII (FVIII) gene (F8). Treatment with recombinant or plasma-derived FVIII replacement therapy is standard therapy. A major problem in treating hemophilia A patients with therapeutic FVIII is that 20% to 30% of these patients produce neutralizing anti-FVIII antibodies (inhibitors) because they are not immunologically tolerant to this human protein. Hence, there is a need to establish tolerogenic protocols to FVIII epitopes. To specifically target FVIII-specific B cells, we engineered immunodominant FVIII domains (A2 and C2) as a chimeric antigen receptor expressed by both human and murine cytotoxic T cells. This FVIII domain engineered B-cell antibody receptor (BAR) that expresses T cells was capable of killing FVIII-reactive B-cell hybridomas in vitro and in vivo. Moreover, FVIII BAR CD8 T cells blocked the development of specific antibody from unimmunized spleen cells stimulated polyclonally with lipopolysaccharide in vitro. In addition, adoptive transfer of FVIII A2- and C2-BAR CD8 T cells significantly reduced the anti-FVIII antibody formation in hemophilic mice. These data suggest that BAR-engineered T cells are a promising approach for future prophylactic treatment for patients with severe hemophilia A who are at high risk of developing inhibitors.

scholarly journals The Current Researches on T Follicular Helper Cells and Associated Diseases

2012 ◽  
Vol 2 (2) ◽  
pp. 85-91
Author(s):  
Jianwei Zhou ◽  
Cui Kong
Keyword(s):  
T Cells ◽  
T Cell ◽  
Autoimmune Disease ◽  
Infectious Diseases ◽  
B Cell ◽  
Humoral Immunity ◽  
Cd4 T Cell ◽  
T Follicular Helper Cells ◽  
Tfh Cells ◽  
Follicular Helper

T follicular helper (Tfh) cell is a new subpopulation of CD4+ T cell family, whose differentiation is affected by Bcl-6, Blimp-1, STAT3, STAT5 and so on, and it could affect or decide the development of other subsets of CD4+ T cells. The important function of Tfh cell is  to help B cell mediate humoral immunity, many researches have proved that Tfh cells participate in the development of autoimmune disease, immunodeficient disease, tumor and    infectious diseases. DOI: http://dx.doi.org/10.3329/jemc.v2i2.12843 J Enam Med Col 2012; 2(2): 85-91

Heme regulates B-cell differentiation, antibody class switch, and heme oxygenase-1 expression in B cells as a ligand of Bach2

Blood ◽  
2011 ◽  
Vol 117 (20) ◽  
pp. 5438-5448 ◽  
Author(s):  
Miki Watanabe-Matsui ◽  
Akihiko Muto ◽  
Toshitaka Matsui ◽  
Ari Itoh-Nakadai ◽  
Osamu Nakajima ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
B Cells ◽  
B Cell ◽  
Heme Oxygenase ◽  
Plasma Cell ◽  
Heme Oxygenase 1 ◽  
Plasma Cell Differentiation ◽  
Class Switch ◽  
Antibody Class

Abstract Heme binds to proteins to modulate their function, thereby functioning as a signaling molecule in a variety of biologic events. We found that heme bound to Bach2, a transcription factor essential for humoral immunity, including antibody class switch. Heme inhibited the DNA binding activity of Bach2 in vitro and reduced its half-life in B cells. When added to B-cell primary cultures, heme enhanced the transcription of Blimp-1, the master regulator of plasma cells, and skewed plasma cell differentiation toward the IgM isotype, decreasing the IgG levels in vitro. Intraperitoneal injection of heme in mice inhibited the production of antigen-specific IgM when heme was administered simultaneously with the antigen but not when it was administered after antigen exposure, suggesting that heme also modulates the early phase of B-cell responses to antigen. Heme oxygenase-1, which is known to be regulated by heme, was repressed by both Bach2 and Bach1 in B cells. Furthermore, the expression of genes for heme uptake changed in response to B-cell activation and heme administration. Our results reveal a new function for heme as a ligand of Bach2 and as a modulatory signal involved in plasma cell differentiation.

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