Role of antigen-presenting cells in the polarized development of helper T cell subsets: evidence for differential cytokine production by Th0 cells in response to antigen presentation by B cells and macrophages

1994 ◽  
Vol 24 (10) ◽  
pp. 2506-2514 ◽  
Author(s):  
David D. Duncan ◽  
Susan L. Swain
Keyword(s):  
T Cell ◽  
B Cells ◽  
Antigen Presentation ◽  
Cytokine Production ◽  
Antigen Presenting Cells ◽  
T Cell Subsets ◽  
Helper T Cell ◽  
Antigen Presenting

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 Small B cells as antigen-presenting cells in the induction of tolerance to soluble protein antigens.

1992 ◽  
Vol 175 (1) ◽  
pp. 131-138 ◽  
Author(s):  
E E Eynon ◽  
D C Parker
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cells ◽  
Soluble Protein ◽  
Antigen Presenting Cells ◽  
Scid Mice ◽  
Protein Antigens ◽  
Helper T Cell ◽  
Cell Compartment ◽  
Antigen Presenting

We have investigated the ability of resting B cells, acting as antigen-presenting cells, to induce tolerance to soluble protein antigens in mice, using an antigen targeted specifically to B cells. We inject mice intravenously with ultracentrifuged Fab fragments of rabbit anti-mouse immunoglobulin D (IgD) (Fab anti-delta). Treatment with Fab anti-delta results in profound tolerance to challenge with 100 micrograms Fab nonimmune rabbit Ig (Fab NRG), precipitated in alum, as measured by antibody production. Tolerance to rabbit Fab is antigen specific, since the treated mice make normal antibody responses to a control antigen, chicken Ig. Tolerance is dependent on antigen presentation by B cells, since intravenous injection of soluble Fab NRG, which is not targeted to B cells, results in a much lower frequency and degree of tolerance, especially at lower doses. T cell help in this system is affected, since T cells from Fab anti-delta-treated mice fail to provide help for an adoptive primary antibody response to Fab NRG when transferred together with normal B cells into severe combined immunodeficient (SCID) mice. The antigen-specific B cell compartment is also affected during tolerance induction, since B cells from treated animals make less antibody than normal B cells when transferred into SCID mice with normal T cells. Although the mechanism of nonresponsiveness in the helper T cell compartment remains to be determined, we think it is likely that the precursors of helper T cells are inactivated or deleted by encountering antigen presented by small, resting B cells, which lack accessory signals necessary to induce helper T cell proliferation and differentiation to effector function.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Role of B cells in maintaining helper T–cell memory

2000 ◽  
Vol 355 (1395) ◽  
pp. 351-355 ◽  
Author(s):  
Dominic van Essen ◽  
Per Dullforce ◽  
David Gray
Keyword(s):  
T Cell ◽  
B Cells ◽  
Antigen Presentation ◽  
T Cell Memory ◽  
Cellular Interactions ◽  
T Cell Epitopes ◽  
Helper T Cell ◽  
Cell Memory

The cellular interactions involved in maintaining CD4 + T–cell memory have hitherto not been identified. In this report, we have investigated the role played by B cells in this process. We show that that longlasting helper T–cell memory depends on the presence of B cells, but that direct antigen presentation by B cells is not required. These findings provide new insights into the mechanisms which underlie helper T–cell memory. They also suggest that the efficacy of future vaccines will depend critically on the inclusion of B– as well as T–cell epitopes.

scholarly journals Ubiquitination by March-I prevents MHC class II recycling and promotes MHC class II turnover in antigen-presenting cells

2015 ◽  
Vol 112 (33) ◽  
pp. 10449-10454 ◽  
Author(s):  
Kyung-Jin Cho ◽  
Even Walseng ◽  
Satoshi Ishido ◽  
Paul A. Roche
Keyword(s):  
B Cells ◽  
Antigen Presentation ◽  
Mhc Class Ii ◽  
Antigen Presenting Cells ◽  
Class Ii ◽  
Mhc Ii ◽  
Class Ii Mhc ◽  
Subsequent Degradation ◽  
Antigen Presenting

MHC class II (MHC-II)-dependent antigen presentation by antigen-presenting cells (APCs) is carefully controlled to achieve specificity of immune responses; the regulated assembly and degradation of antigenic peptide–MHC-II complexes (pMHC-II) is one aspect of such control. In this study, we have examined the role of ubiquitination in regulating pMHC-II biosynthesis, endocytosis, recycling, and turnover in APCs. By using APCs obtained from MHC-II ubiquitination mutant mice, we find that whereas ubiquitination does not affect pMHC-II formation in dendritic cells (DCs), it does promote the subsequent degradation of newly synthesized pMHC-II. Acute activation of DCs or B cells terminates expression of the MHC-II E3 ubiquitin ligase March-I and prevents pMHC-II ubiquitination. Most importantly, this change results in very efficient pMHC-II recycling from the surface of DCs and B cells, thereby preventing targeting of internalized pMHC-II to lysosomes for degradation. Biochemical and functional assays confirmed that pMHC-II turnover is suppressed in MHC-II ubiquitin mutant DCs or by acute activation of wild-type DCs. These studies demonstrate that acute APC activation blocks the ubiquitin-dependent turnover of pMHC-II by promoting efficient pMHC-II recycling and preventing lysosomal targeting of internalized pMHC-II, thereby enhancing pMHC-II stability for efficient antigen presentation to CD4 T cells.

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.

Abstract 252: Interleukin-27 Signaling Regulates Myeloid Cells Activation in Atherosclerosis

2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
Iuliia Peshkova ◽  
Aliia Fatkhullina ◽  
Ekaterina Koltsova
Keyword(s):  
T Cells ◽  
T Cell ◽  
Inflammatory Cytokines ◽  
Antigen Presenting Cells ◽  
Atherosclerotic Lesions ◽  
Mediators Of Inflammation ◽  
Antigen Presenting ◽  
Deficient Mice ◽  
Pro Inflammatory Cytokines

Atherosclerosis is a lipid-driven inflammatory disease characterized by the progressive plaque growth in the vessels. Cytokines are important mediators of inflammation and atherosclerosis. While pro-inflammatory cytokines were extensively investigated, little is known about the role of anti-inflammatory cytokines as to their ability to control vascular inflammation. We tested whether immunoregulatory IL-27R signaling is important to control inflammation in mouse models of atherosclerosis. We found that atherosclerosis-prone mice with hematopoietic deficiency of IL-27R ( Ldlr -/- mice reconstituted with bone marrow from Il27ra -/- ) or global deficiency ( Il27ra -/- x Apoe -/- ) developed significantly larger atherosclerotic lesions compared to controls. Atherosclerotic lesions in IL-27R deficient mice contained more CD45 + leukocytes and CD4 + T cells, which produced pro-atherogenic cytokines IL-17A and TNF-α. These cytokines normally suppressed by IL-27, regulated the expression of CCL2 and other chemokines, which in turn led to accumulation of myeloid CD11b + and CD11c + cells in atherosclerotic aortas. Using two-photon microscopy, we found enhanced interactions between antigen presenting cells and T cells in the aortas of IL-27R deficient mice accompanied by enhanced CD4 T cell proliferation. Moreover, macrophages in Il27ra -/- aortas also demonstrated enhanced ability to produce pro-inflammatory cytokines, including IL-1. The blockade of IL-1R signaling, however, strongly suppressed atherosclerosis progression in IL-27R deficient but not control mice, suggesting an important role of IL-27 in the regulation of IL-1 production in atherosclerosis. Overall, our data demonstrate that IL-27R signaling in atherosclerosis is required to control function of antigen presenting cells modulating subsequent T cell activation in the aortas. Moreover, it controls macrophage activation and pro-inflammatory myeloid cell-derived cytokine production. These mechanisms altogether curb pathogenic T cell lineage differentiation and, thus, atherosclerosis, suggesting potent anti-atherogenic role of IL-27.

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