scholarly journals Antigen-presenting ILC3 regulate T cell–dependent IgA responses to colonic mucosal bacteria

2019 ◽  
Vol 216 (4) ◽  
pp. 728-742 ◽  
Author(s):  
Felipe Melo-Gonzalez ◽  
Hana Kammoun ◽  
Elza Evren ◽  
Emma E. Dutton ◽  
Markella Papadopoulou ◽  
...  
Keyword(s):  
T Cell ◽  
B Cells ◽  
Antigen Presentation ◽  
Immunoglobulin A ◽  
Lymphoid Cells ◽  
Host Interactions ◽  
Commensal Microbiota ◽  
Follicular Helper ◽  
Cell Class ◽  
Antigen Presenting

Intestinal immune homeostasis is dependent upon tightly regulated and dynamic host interactions with the commensal microbiota. Immunoglobulin A (IgA) produced by mucosal B cells dictates the composition of commensal bacteria residing within the intestine. While emerging evidence suggests the majority of IgA is produced innately and may be polyreactive, mucosal-dwelling species can also elicit IgA via T cell–dependent mechanisms. However, the mechanisms that modulate the magnitude and quality of T cell–dependent IgA responses remain incompletely understood. Here we demonstrate that group 3 innate lymphoid cells (ILC3) regulate steady state interactions between T follicular helper cells (TfH) and B cells to limit mucosal IgA responses. ILC3 used conserved migratory cues to establish residence within the interfollicular regions of the intestinal draining lymph nodes, where they act to limit TfH responses and B cell class switching through antigen presentation. The absence of ILC3-intrinsic antigen presentation resulted in increased and selective IgA coating of bacteria residing within the colonic mucosa. Together these findings implicate lymph node resident, antigen-presenting ILC3 as a critical regulatory checkpoint in the generation of T cell–dependent colonic IgA and suggest ILC3 act to maintain tissue homeostasis and mutualism with the mucosal-dwelling commensal microbiota.

scholarly journals Abortive Proliferation of Rare T Cells Induced by Direct or Indirect Antigen Presentation by Rare B Cells In Vivo

1998 ◽  
Vol 187 (10) ◽  
pp. 1611-1621 ◽  
Author(s):  
Sarah E. Townsend ◽  
Christopher C. Goodnow
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cells ◽  
Antigen Presentation ◽  
Cell Fate ◽  
T Cell Activation ◽  
Cell Activation ◽  
Antigen Presenting Cells ◽  
Antigen Presenting

Antigen-specific B cells are implicated as antigen-presenting cells in memory and tolerance responses because they capture antigens efficiently and localize to T cell zones after antigen capture. It has not been possible, however, to visualize the effect of specific B cells on specific CD4+ helper T cells under physiological conditions. We demonstrate here that rare T cells are activated in vivo by minute quantities of antigen captured by antigen-specific B cells. Antigen-activated B cells are helped under these conditions, whereas antigen-tolerant B cells are killed. The T cells proliferate and then disappear regardless of whether the B cells are activated or tolerant. We show genetically that T cell activation, proliferation, and disappearance can be mediated either by transfer of antigen from antigen-specific B cells to endogenous antigen-presenting cells or by direct B–T cell interactions. These results identify a novel antigen presentation route, and demonstrate that B cell presentation of antigen has profound effects on T cell fate that could not be predicted from in vitro studies.

scholarly journals Antigen presentation by resting B cells. Radiosensitivity of the antigen-presentation function and two distinct pathways of T cell activation.

1984 ◽  
Vol 159 (3) ◽  
pp. 881-905 ◽  
Author(s):  
J D Ashwell ◽  
A L DeFranco ◽  
W E Paul ◽  
R H Schwartz
Keyword(s):  
Cell Proliferation ◽  
T Cells ◽  
T Cell ◽  
B Cells ◽  
B Cell ◽  
Antigen Presentation ◽  
Cell Activation ◽  
T Cell Proliferation ◽  
B Cell Activation ◽  
Antigen Presenting

In this report we have examined the ability of small resting B cells to act as antigen-presenting cells (APC) to antigen-specific MHC-restricted T cells as assessed by either T cell proliferation or T cell-dependent B cell stimulation. We found that 10 of 14 in vitro antigen-specific MHC-restricted T cell clones and lines and three of four T cell hybridomas could be induced to either proliferate or secrete IL-2 in the presence of lightly irradiated (1,000 rads) purified B cells and the appropriate foreign antigen. All T cell lines and hybridomas were stimulated to proliferate or make IL-2 by macrophage- and dendritic cell-enriched populations and all T cells tested except one hybridoma caused B cell activation when stimulated with B cells as APC. Furthermore, lightly irradiated, highly purified syngeneic B cells were as potent a source of APC for inducing B cell activation as were low density dendritic and macrophage-enriched cells. Lymph node T cells freshly taken from antigen-primed animals were also found to proliferate when cultured with purified B cells and the appropriate antigen. Thus, small resting B cells can function as APC to a variety of T cells. This APC function was easily measured when the cells were irradiated with 1,000 rads, but was greatly diminished or absent when they were irradiated with 3,300 rads. Thus, the failure of some other laboratories to observe this phenomenon may be the result of the relative radiosensitivity of the antigen-presenting function of the B cells. In addition, this radiosensitivity allowed us to easily distinguish B cell antigen presentation from presentation by the dendritic cell and macrophage, as the latter was resistant to 3,300 rads. Finally, one T cell clone that failed to proliferate when B cells were used as APC was able to recruit allogeneic B cells to proliferate in the presence of syngeneic B cells and the appropriate antigen. This result suggests that there are at least two distinct pathways of activation in T cells, one that leads to T cell proliferation and one that leads to the secretion of B cell recruitment factor(s).

scholarly journals Induction of Peripheral T Cell Tolerance by Antigen-Presenting B Cells. II. Chronic Antigen Presentation Overrules Antigen-Presenting B Cell Activation

2006 ◽  
Vol 176 (7) ◽  
pp. 4021-4028 ◽  
Author(s):  
Giorgio Raimondi ◽  
Ivan Zanoni ◽  
Stefania Citterio ◽  
Paola Ricciardi-Castagnoli ◽  
Francesca Granucci
Keyword(s):  
T Cell ◽  
B Cells ◽  
B Cell ◽  
Antigen Presentation ◽  
Cell Activation ◽  
T Cell Tolerance ◽  
Cell Tolerance ◽  
B Cell Activation ◽  
Antigen Presenting

scholarly journals Induction of Peripheral T Cell Tolerance by Antigen-Presenting B Cells. I. Relevance of Antigen Presentation Persistence

2006 ◽  
Vol 176 (7) ◽  
pp. 4012-4020 ◽  
Author(s):  
Giorgio Raimondi ◽  
Ivan Zanoni ◽  
Stefania Citterio ◽  
Paola Ricciardi-Castagnoli ◽  
Francesca Granucci
Keyword(s):  
T Cell ◽  
B Cells ◽  
Antigen Presentation ◽  
T Cell Tolerance ◽  
Cell Tolerance ◽  
Antigen Presenting

scholarly journals Tumorantigen-Specific CD40B Cells: Combining Enhanced Antigen-Presentation and Antibody-Secretion for Tumor Targeting

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 1030-1030
Author(s):  
Kerstin Wennhold ◽  
Martin Thelen ◽  
Maria gracia Marquez ◽  
Christof Scheid ◽  
Alexander Shimabukuro-Vornhagen ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
T Cell ◽  
B Cells ◽  
Antigen Presentation ◽  
Board Of Directors ◽  
Plasma Cells ◽  
Cd8 T Cell ◽  
Advisory Committees ◽  
Antigen Presenting

Abstract Efficient antigen presentation is a prerequisite for the development of a T-cell-mediated immune response. Dendritic cells (DCs) are the most prominent professional antigen-presenting cells (APCs). However, they have several disadvantages as cellular adjuvant in cancer immunotherapy. Therefore, an alternative approach was developed, in which polyclonal B cells can serve as potent APCs by treatment with the CD40 ligand. We demonstrated that CD40-activation dramatically improves antigen presentation by B cells, efficiently inducing naive and memory CD4+ and CD8+ T-cell responses. Moreover, these CD40-activated (CD40) B cells home to secondary lymphoid organs. However, antigen presentation by antigen-specific B cells is more effective compared to polyclonal B cells. Therefore, we use tumorantigen-specific B cells to improve the antigen-presenting function of CD40B cells. Purified human and murine tumorantigen-specific B cells highly upregulate activation markers upon CD40-stimulation, which results in an enhanced CD4+ and CD8+ T cell response in vitro and in vivo. This response is significantly lower in polyclonal CD40B cells and comparable to the stimulation induced by mature dendritic cells. Moreover, antigen-specific B cells could be stimulated in vitro to differentiate into antibody-secreting plasma cells. Treatment of E.G7 lymphoma-bearing mice with a combination of antigen-specific CD40B cells and plasma cells results in inhibition of tumor growth and prolonged survival. Moreover, antigen-specific B cells home to the tumor site and the spleen, where they encounter T cells. These results provide new insights into the role of activated antigen-specific B cells as APCs and their use for cancer immunotherapy. Disclosures Scheid: Janssen-Cilag: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees.

scholarly journals Glatiramer acetate immune modulates B-cell antigen presentation in treatment of MS

2020 ◽  
Vol 7 (3) ◽  
pp. e698 ◽  
Author(s):  
Darius Häusler ◽  
Zivar Hajiyeva ◽  
Jan W. Traub ◽  
Scott S. Zamvil ◽  
Patrice H. Lalive ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cells ◽  
B Cell ◽  
Antigen Presentation ◽  
Glatiramer Acetate ◽  
Mhc Class Ii ◽  
Class Ii ◽  
Cell Antigen ◽  
Antigen Presenting

ObjectiveWe examined the effect of glatiramer acetate (GA) on B-cell maturation, differentiation, and antigen presentation in MS and experimental autoimmune encephalomyelitis (EAE).MethodsA cross-sectional study of blood samples from 20 GA-treated and 18 untreated patients with MS was performed by flow cytometry; 6 GA-treated patients with MS were analyzed longitudinally. GA-mediated effects on B-cell antigen-presenting function were investigated in EAE, or, alternatively, B cells were treated with GA in vitro using vehicle as a control.ResultsIn MS, GA diminished transitional B-cell and plasmablast frequency, downregulated CD69, CD25, and CD95 expression, and decreased TNF-α production, whereas IL-10 secretion and MHC Class II expression were increased. In EAE, we observed an equivalent dampening of proinflammatory B-cell properties and an enhanced expression of MHC Class II. When used as antigen-presenting cells for activation of naive T cells, GA-treated B cells promoted development of regulatory T cells, whereas proinflammatory T-cell differentiation was diminished.ConclusionsGA immune modulates B-cell function in EAE and MS and efficiently interferes with pathogenic B cell–T cell interaction.

scholarly journals Efficient T cell–B cell collaboration guides autoantibody epitope bias and onset of celiac disease

2019 ◽  
Vol 116 (30) ◽  
pp. 15134-15139 ◽  
Author(s):  
Rasmus Iversen ◽  
Bishnudeo Roy ◽  
Jorunn Stamnaes ◽  
Lene S. Høydahl ◽  
Kathrin Hnida ◽  
...  
Keyword(s):  
T Cells ◽  
Celiac Disease ◽  
T Cell ◽  
B Cells ◽  
B Cell ◽  
Antigen Presentation ◽  
Disease Onset ◽  
Antigen Presenting Cells ◽  
Autoantibody Production ◽  
Antigen Presenting

B cells play important roles in autoimmune diseases through autoantibody production, cytokine secretion, or antigen presentation to T cells. In most cases, the contribution of B cells as antigen-presenting cells is not well understood. We have studied the autoantibody response against the enzyme transglutaminase 2 (TG2) in celiac disease patients by generating recombinant antibodies from single gut plasma cells reactive with discrete antigen domains and by undertaking proteomic analysis of anti-TG2 serum antibodies. The majority of the cells recognized epitopes in the N-terminal domain of TG2. Antibodies recognizing C-terminal epitopes interfered with TG2 cross-linking activity, and B cells specific for C-terminal epitopes were inefficient at taking up TG2-gluten complexes for presentation to gluten-specific T cells. The bias toward N-terminal epitopes hence reflects efficient T-B collaboration. Production of antibodies against N-terminal epitopes coincided with clinical onset of disease, suggesting that TG2-reactive B cells with certain epitope specificities could be the main antigen-presenting cells for pathogenic, gluten-specific T cells. The link between B cell epitopes, antigen presentation, and disease onset provides insight into the pathogenic mechanisms of a T cell-mediated autoimmune condition.

scholarly journals Gut T cell–independent IgA responses to commensal bacteria require engagement of the TACI receptor on B cells

2020 ◽  
Vol 5 (49) ◽  
pp. eaat7117 ◽  
Author(s):  
E. K. Grasset ◽  
A. Chorny ◽  
S. Casas-Recasens ◽  
C. Gutzeit ◽  
G. Bongers ◽  
...  
Keyword(s):  
T Cell ◽  
B Cells ◽  
Gut Microbiota ◽  
B Cell ◽  
Immunoglobulin A ◽  
Cd40 Ligand ◽  
Commensal Bacteria ◽  
Secretory Immunoglobulin A ◽  
Follicular Helper ◽  
Secretory Immunoglobulin

The gut mounts secretory immunoglobulin A (SIgA) responses to commensal bacteria through nonredundant T cell–dependent (TD) and T cell–independent (TI) pathways that promote the establishment of mutualistic host-microbiota interactions. SIgAs from the TD pathway target penetrant bacteria, and their induction requires engagement of CD40 on B cells by CD40 ligand on T follicular helper cells. In contrast, SIgAs from the TI pathway bind a larger spectrum of bacteria, but the mechanism underpinning their production remains elusive. Here, we show that the intestinal TI pathway required CD40-independent B cell–activating signals from TACI, a receptor for the innate CD40 ligand–like factors BAFF and APRIL. TACI-induced SIgA responses targeted a fraction of the gut microbiota without shaping its overall composition. Of note, TACI was dispensable for TD induction of IgA in gut-associated lymphoid organs. Thus, BAFF/APRIL signals acting on TACI orchestrate commensal bacteria–specific SIgA responses through an intestinal TI program.

scholarly journals B cell residency but not T cell–independent IgA switching in the gut requires innate lymphoid cells

2021 ◽  
Vol 118 (27) ◽  
pp. e2106754118
Author(s):  
Mingzhu Zheng ◽  
Kairui Mao ◽  
Difeng Fang ◽  
Dan Li ◽  
Jun Lyu ◽  
...  
Keyword(s):  
T Cell ◽  
B Cells ◽  
B Cell ◽  
Plasma Cells ◽  
Immunoglobulin A ◽  
Innate Lymphoid Cells ◽  
Lymphoid Cells ◽  
Lymphoid Structures ◽  
Iga Production ◽  
Cell Adoptive Transfer

Immunoglobulin A (IgA)–producing plasma cells derived from conventional B cells in the gut play an important role in maintaining the homeostasis of gut flora. Both T cell–dependent and T cell–independent IgA class switching occurs in the lymphoid structures in the gut, whose formation depends on lymphoid tissue inducers (LTis), a subset of innate lymphoid cells (ILCs). However, our knowledge on the functions of non-LTi helper-like ILCs, the innate counter parts of CD4 T helper cells, in promoting IgA production is still limited. By cell adoptive transfer and utilizing a unique mouse strain, we demonstrated that the generation of IgA-producing plasma cells from B cells in the gut occurred efficiently in the absence of both T cells and helper-like ILCs and without engaging TGF-β signaling. Nevertheless, B cell recruitment and/or retention in the gut required functional NKp46−CCR6+ LTis. Therefore, while CCR6+ LTis contribute to the accumulation of B cells in the gut through inducing lymphoid structure formation, helper-like ILCs are not essential for the T cell–independent generation of IgA-producing plasma cells.

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