scholarly journals Regulation of Alloantibody Responses

2021 ◽  
Vol 9 ◽  
Author(s):  
Anita S. Chong ◽  
Peter T. Sage ◽  
Maria-Luisa Alegre
Keyword(s):  
T Cells ◽  
B Cells ◽  
De Novo ◽  
Transplant Rejection ◽  
Treg Cells ◽  
Effector Cells ◽  
Follicular Helper ◽  
Alloreactive T Cells ◽  
New Findings ◽  
Antigen Presenting

The control of alloimmunity is essential to the success of organ transplantation. Upon alloantigen encounter, naïve alloreactive T cells not only differentiate into effector cells that can reject the graft, but also into T follicular helper (Tfh) cells that promote the differentiation of alloreactive B cells that produce donor-specific antibodies (DSA). B cells can exacerbate the rejection process through antibody effector functions and/or B cell antigen-presenting functions. These responses can be limited by immune suppressive mechanisms mediated by T regulatory (Treg) cells, T follicular regulatory (Tfr) cells, B regulatory (Breg) cells and a newly described tolerance-induced B (TIB) cell population that has the ability to suppress de novo B cells in an antigen-specific manner. Transplantation tolerance following costimulation blockade has revealed mechanisms of tolerance that control alloreactive T cells through intrinsic and extrinsic mechanisms, but also inhibit alloreactive B cells. Thus, the control of both arms of adaptive immunity might result in more robust tolerance, one that may withstand more severe inflammatory challenges. Here, we review new findings on the control of B cells and alloantibody production in the context of transplant rejection and tolerance.

scholarly journals Co-stimulatory function in primary germinal center responses: CD40 and B7 are required on distinct antigen-presenting cells

2017 ◽  
Vol 214 (9) ◽  
pp. 2795-2810 ◽  
Author(s):  
Masashi Watanabe ◽  
Chiharu Fujihara ◽  
Andrea J. Radtke ◽  
Y. Jeffrey Chiang ◽  
Sumeena Bhatia ◽  
...  
Keyword(s):  
T Cells ◽  
B Cells ◽  
Germinal Center ◽  
Helper T Cells ◽  
Vaccine Responses ◽  
High Affinity ◽  
Prevailing Paradigm ◽  
Follicular Helper ◽  
Cd40 Expression ◽  
Antigen Presenting

T cell–dependent germinal center (GC) responses require coordinated interactions of T cells with two antigen-presenting cell (APC) populations, B cells and dendritic cells (DCs), in the presence of B7- and CD40-dependent co-stimulatory pathways. Contrary to the prevailing paradigm, we found unique cellular requirements for B7 and CD40 expression in primary GC responses to vaccine immunization with protein antigen and adjuvant: B7 was required on DCs but was not required on B cells, whereas CD40 was required on B cells but not on DCs in the generation of antigen-specific follicular helper T cells, antigen-specific GC B cells, and high-affinity class-switched antibody production. There was, in fact, no requirement for coexpression of B7 and CD40 on the same cell in these responses. Our findings support a substantially revised model for co-stimulatory function in the primary GC response, with crucial and distinct contributions of B7- and CD40-dependent pathways expressed by different APC populations and with important implications for understanding how to optimize vaccine responses or limit autoimmunity.

scholarly journals IL-Y Aggravates Murine Chronic Graft-Versus-Host Disease by Enhancing T and B Cell Responses

2020 ◽  
Vol 11 ◽  
Author(s):  
Li Wan ◽  
Ziqi Jin ◽  
Bo Hu ◽  
Kangkang Lv ◽  
Lei Lei ◽  
...  
Keyword(s):  
T Cells ◽  
B Cells ◽  
B Cell ◽  
Treg Cells ◽  
Host Disease ◽  
Mhc Ii ◽  
Follicular Helper ◽  
Tnf Α ◽  
Dsdna Antibody ◽  
Il Y A

IL-Y, a synthetic member of IL-12 cytokine family, was found to exert potent immunosuppressive effects by inhibiting the differentiation and activation of Th1 and Th17 cells. However, the role of IL-Y in the development of chronic graft-versus-host disease (cGVHD) remains unknown. Here, using murine models of scleroderma-like and lupus-like cGVHD, we examined the function of IL-Y in the pathogenesis of cGVHD by hydrodynamically injecting minicircle-IL-Y expressing plasmids (MC IL-Y). In contrast with the reported immune suppressive function of IL-Y, administration of MC IL-Y enhanced cGVHD severity reflected by deteriorated multi-organ pathologic damages. In lupus-like cGVHD model, urine protein and the serum anti-dsDNA antibody (IgG) were significantly upregulated by IL-Y treatment. Further study demonstrated that IL-Y impacts both donor T and B cell response. In T cells, IL-Y inhibited the generation of CD4+Foxp3+ regulator T (Treg) cells during the development of cGVHD. IL-Y may also increase the infiltration of pathogenic TNF-α producing CD4+ and CD8+ T cells through IL-27Rα in recipient spleens, as this effect was diminished in IL-27Rα deficient T cells. Moreover, IL-Y enhanced the differentiation of ICOS+ T follicular helper (Tfh) cells. In B cells, the percentage of germinal center (GC) B cells in recipient spleens was significantly upregulated by MC IL-Y plasmid administration. The levels of co-stimulatory molecules, MHC-II and CD86, on B cells were also enhanced by IL-Y expression. Taken together, our data indicated that IL-Y promoted the process of cGVHD by activating pathogenic T and B cells.

scholarly journals Follicular Helper CD4+ T Cells, Follicular Regulatory CD4+ T Cells, and Inducible Costimulator and Their Roles in Multiple Sclerosis and Experimental Autoimmune Encephalomyelitis

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Xue Zhang ◽  
Ruli Ge ◽  
Hongliang Chen ◽  
Maxwell Ahiafor ◽  
Bin Liu ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
T Cells ◽  
B Cells ◽  
Cd4 T Cells ◽  
B Cell Lymphoma ◽  
Treg Cells ◽  
Effector T Cells ◽  
Tfh Cells ◽  
Follicular Helper ◽  
Inducible Costimulator

Follicular helper CD4+ T (TFH) cells are a specialized subset of effector T cells that play a central role in orchestrating adaptive immunity. TFH cells mainly promote germinal center (GC) formation, provide help to B cells for immunoglobulin affinity maturation and class-switch recombination of B cells, and facilitate production of long-lived plasma cells and memory B cells. TFH cells express the nuclear transcriptional repressor B cell lymphoma 6 (Bcl-6), the chemokine (C-X-C motif) receptor 5 (CXCR5), the CD28 family members programmed cell death protein-1 (PD-1) and inducible costimulator (ICOS) and are also responsible for the secretion of interleukin-21 (IL-21) and IL-4. Follicular regulatory CD4+ T (TFR) cells, as a regulatory counterpart of TFH cells, participate in the regulation of GC reactions. TFR cells not only express markers of TFH cells but also express markers of regulatory T (Treg) cells containing FOXP3, glucocorticoid-induced tumor necrosis factor receptor (GITR), cytotoxic T lymphocyte antigen 4 (CTLA-4), and IL-10, hence owing to the dual characteristic of TFH cells and Treg cells. ICOS, expressed on activated CD4+ effector T cells, participates in T cell activation, differentiation, and effector process. The expression of ICOS is highest on TFH and TFR cells, indicating it as a key regulator of humoral immunity. Multiple sclerosis (MS) is a severe autoimmune disease that affects the central nervous system and results in disability, mediated by autoreactive T cells with evolving evidence of a remarkable contribution from humoral responses. This review summarizes recent advances regarding TFH cells, TFR cells, and ICOS, as well as their functional characteristics in relation to MS.

scholarly journals Distinct Features of Germinal Center Reactions in Macaques Infected by SIV or Vaccinated with a T-Dependent Model Antigen

Viruses ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 263
Author(s):  
Maria Trovato ◽  
Hany M. Ibrahim ◽  
Stephane Isnard ◽  
Roger Le Grand ◽  
Nathalie Bosquet ◽  
...  
Keyword(s):  
T Cells ◽  
B Cells ◽  
Protective Immunity ◽  
Affinity Maturation ◽  
Follicular Helper ◽  
Siv Infection ◽  
Dependent Model ◽  
Low Levels ◽  
Antigen Presenting ◽  
Distinct Features

B-cell follicles constitute large reservoirs of infectious HIV/SIV associated to follicular dendritic cells and infecting follicular helper (TFH) and regulatory (TFR) T-cells in germinal centers (GCs). Thus, follicular and GC B-cells are persistently exposed to viral antigens. Despite recent development of potent HIV immunogens, numerous questions are still open regarding GC reaction during early HIV/SIV infection. Here, we dissect the dynamics of B- and T-cells in GCs of macaques acutely infected by SIV (Group SIV+) or vaccinated with Tetanus Toxoid (Group TT), a T-dependent model antigen. Systemic inflammation and mobilization of antigen-presenting cells in inguinal lymph nodes and spleen are lower in Group TT than in Group SIV+. Despite spleen GC reaction of higher magnitude in Group SIV+, the development of protective immunity could be limited by abnormal helper functions of TFH massively polarized into TFH1-like cells, by inflammation-induced recruitment of fCD8 (either regulatory or cytotoxic) and by low numbers of TFR limiting TFH/TFR competition for high affinity B-cells. Increased GC B-cells apoptosis and accumulation of CD21lo memory B-cells, unable to further participate to GC reaction, likely contribute to eliminate SIV-specific B-cells and decrease antibody affinity maturation. Surprisingly, functional GCs and potent TT-specific antibodies develop despite low levels of CXCL13.

scholarly journals B cell depletion impairs vaccination-induced CD8+ T cell responses in a type I interferon-dependent manner

2021 ◽  
pp. annrheumdis-2021-220435
Author(s):  
Theresa Graalmann ◽  
Katharina Borst ◽  
Himanshu Manchanda ◽  
Lea Vaas ◽  
Matthias Bruhn ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cells ◽  
B Cell ◽  
Cell Expansion ◽  
De Novo ◽  
T Cell Responses ◽  
Type I ◽  
Cell Responses ◽  
T Cell Expansion

ObjectivesThe monoclonal anti-CD20 antibody rituximab is frequently applied in the treatment of lymphoma as well as autoimmune diseases and confers efficient depletion of recirculating B cells. Correspondingly, B cell-depleted patients barely mount de novo antibody responses during infections or vaccinations. Therefore, efficient immune responses of B cell-depleted patients largely depend on protective T cell responses.MethodsCD8+ T cell expansion was studied in rituximab-treated rheumatoid arthritis (RA) patients and B cell-deficient mice on vaccination/infection with different vaccines/pathogens.ResultsRituximab-treated RA patients vaccinated with Influvac showed reduced expansion of influenza-specific CD8+ T cells when compared with healthy controls. Moreover, B cell-deficient JHT mice infected with mouse-adapted Influenza or modified vaccinia virus Ankara showed less vigorous expansion of virus-specific CD8+ T cells than wild type mice. Of note, JHT mice do not have an intrinsic impairment of CD8+ T cell expansion, since infection with vaccinia virus induced similar T cell expansion in JHT and wild type mice. Direct type I interferon receptor signalling of B cells was necessary to induce several chemokines in B cells and to support T cell help by enhancing the expression of MHC-I.ConclusionsDepending on the stimulus, B cells can modulate CD8+ T cell responses. Thus, B cell depletion causes a deficiency of de novo antibody responses and affects the efficacy of cellular response including cytotoxic T cells. The choice of the appropriate vaccine to vaccinate B cell-depleted patients has to be re-evaluated in order to efficiently induce protective CD8+ T cell responses.

A BATF-ling connection between B cells and follicular helper T cells

2011 ◽  
Vol 12 (6) ◽  
pp. 519-520 ◽  
Author(s):  
Julia I Ellyard ◽  
Carola G Vinuesa
Keyword(s):  
T Cells ◽  
B Cells ◽  
Helper T Cells ◽  
Follicular Helper T Cells ◽  
Follicular Helper

scholarly journals The autoantigen-binding B cell repertoires of normal and of chronically graft-versus-host-diseased mice.

1987 ◽  
Vol 165 (6) ◽  
pp. 1675-1687 ◽  
Author(s):  
A G Rolink ◽  
T Radaszkiewicz ◽  
F Melchers
Keyword(s):  
T Cells ◽  
B Cells ◽  
B Cell ◽  
The Other ◽  
Cell Populations ◽  
Foreign Antigen ◽  
Alloreactive T Cells ◽  
Polyclonal Activator ◽  
Activated B Cells

A quantitative analysis of the frequencies of autoantibody-producing B cells in GVHD and in normal mice has been undertaken by generating collections of hybridomas of activated B cells. These hybridomas secreted sufficient quantities of Ig to allow binding analyses on a panel of autoantigens. B cells have been activated in a variety of ways. In vivo they were activated by injection of alloreactive T cells of one parent, leading to GVHD by a foreign antigen, sheep erythrocytes, in a secondary response, or by the polyclonal activator LPS. B cells from an experimentally unstimulated animal were used for an analysis of the normal background. In vitro B cells were activated by alloreactive T cells or by LPS. The frequencies of hybridomas and, therefore, of activated B cells producing autoantibodies to DNA or to kidney were not significantly different in mice activated by a graft-vs.-host T cell response as compared with B cell populations activated by any of the other procedures. They were found to compose 7.1-17.1% of the total repertoire of activated B cells. Moreover, the frequencies of autoantibody-producing activated B cells does not change with time after induction of the graft-vs.-host reaction. The pattern and frequencies of autoantigen-binding specificities to cytoskeleton, smooth muscle, nuclei, mitochondria, and DNA were not found to be different in any of the groups of hybridomas. The single notable exception, found in GVHD mice, were hybridomas producing autoantibodies to kidney proximal tubular brush border. These results allow the conclusion that autoantigen-binding B cells exist in an activated state in GVHD mice, as well as in mice activated by a foreign antigen or by a polyclonal activator, in B cell populations activated in vitro either by alloreactive T cells or by a polyclonal activator, and even in the background of experimentally unstimulated animals. T cell-mediated graft-vs.-host activation, in large part, does not lead to a selective expansion of autoantigen-binding B cells. The main difference between the graft-vs.-host-activated B cell repertoire and all others is that approximately 90% of teh autoantibodies were of the IgG class, whereas al autoantibodies found in the other groups were IgM.

scholarly journals CD1c but neither CD1a nor CD1b molecules are expressed on normal, activated, and malignant human B cells: identification of a new B-cell subset

Blood ◽  
1988 ◽  
Vol 72 (1) ◽  
pp. 241-247 ◽  
Author(s):  
D Delia ◽  
G Cattoretti ◽  
N Polli ◽  
E Fontanella ◽  
A Aiello ◽  
...  
Keyword(s):  
T Cells ◽  
B Cells ◽  
B Cell ◽  
De Novo ◽  
Cell Subset ◽  
Ultrastructural Level ◽  
Cytoplasmic Staining ◽  
Clear Cut ◽  
Hodgkin's Lymphomas

Abstract The CD1 cluster of monoclonal antibodies (MoAbs) CD1a, CD1b, and CD1c, identifies molecules that are differentially expressed on hematopoietic and nonhematopoietic tissues. Our earlier finding that the mantle zone (MZ) but not the germinal center (GC) of normal lymph nodes (LN) is CD1c+, CD1a-, and CD1b- prompted us to further investigate the expression of these molecules on normal, activated, and malignant B cells. We report that blood and spleen contain CD1c+ B cells that account for 49% +/- 20.4% (mean +/- SD) and 50.9% +/- 4.4% of the total B cell population, respectively. CD1a- and CD1b-specific MoAbs are unreactive with both B and T cells; these latter are CD1c- as well. When CD1c+ and CD1c- B cells are activated in vitro, the CD1c molecule is upregulated in the former subset and induced de novo in the latter. Conversely, activated blood T cells remain CD1c-. Neither CD1a nor CD1b molecules are detected on activated T and B lymphocytes. At ultrastructural level, the CD1c+ B cells exhibit distinctive features, namely, condensed chromatin with or without a nucleolus and a unique cluster of cytoplasmic vesicles and organelles; the number of nucleolated cells is higher in the spleen (95%) than in the tonsil (40%) or blood (5%). These findings further confirm the similarity between blood and MZ B cells. The CD1c expression assessed on 27 B-cell chronic lymphocytic leukemias (B-CLL) and 46 B non-Hodgkin's lymphomas (B-NHL) was detected on 41% and 32% of cases, respectively; the latter comprised four follicular and 11 diffuse histotypes. The Burkitt's lymphomas were CD1c-negative. The B-cell neoplasms were all CD1a- and, except for four with a weak cytoplasmic staining, all CD1b- as well. The clear-cut CD1c distribution in normal LN (MZ+, GC-) contrasted with the evidence that some B-NHL cells of GC origin (eg, follicular with predominantly small cleaved cells) were CD1c+. Overall, the finding that CD1c expression is restricted to a fraction of B cells present in lymphoid organs and in peripheral blood indicates that CD1c is a powerful marker for the identification and dissection of B-cell subsets whose functional properties can now be evaluated.

scholarly journals Differential immune cell infiltrations between healthy periodontal and chronic periodontitis tissues

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Wei Li ◽  
Zheng Zhang ◽  
Zuo-min Wang
Keyword(s):  
T Cells ◽  
B Cells ◽  
Mast Cells ◽  
Plasma Cells ◽  
Immune Cell ◽  
Memory T Cells ◽  
Host Immunity ◽  
Memory B Cells ◽  
Helper T Cells ◽  
Follicular Helper

Abstract Background Host immunity plays an important role against oral microorganisms in periodontitis. Methods This study assessed the infiltrating immune cell subtypes in 133 healthy periodontal and 210 chronic periodontitis tissues from Gene Expression Omnibus (GEO) datasets using the CIBERSORT gene signature files. Results Plasma cells, naive B cells and neutrophils were all elevated in periodontitis tissues, when compared to those in healthy controls. In contrast, memory B cells, resting dendritic, mast cells and CD4 memory cells, as well as activated mast cells, M1 and M2 macrophages, and follicular helper T cells, were mainly present in healthy periodontal tissues. Furthermore, these periodontitis tissues generally contained a higher proportion of activated CD4 memory T cells, while the other subtypes of T cells, including resting CD4 memory T cells, CD8 T cells, follicular helper T cells (TFH) and regulatory T cells (Tregs), were relatively lower in periodontitis tissues, when compared to healthy tissues. The ratio of dendritic and mast cells and macrophages was lower in periodontitis tissues, when compared to healthy tissues. In addition, there was a significant negative association of plasma cells with most of the other immune cells, such as plasma cells vs. memory B cells (γ = − 0.84), plasma cells vs. resting dendritic cells (γ = − 0.64), plasma cells vs. resting CD4 memory T cells (γ = 0.50), plasma cells versus activated dendritic cells (γ = − 0.46), plasma cells versus TFH (γ = − 0.46), plasma cells versus macrophage M2 cells (γ = − 0.43), or plasma cells versus macrophage M1 cells (γ = − 0.40), between healthy control and periodontitis tissues. Conclusion Plasma cells, naive B cells and neutrophils were all elevated in periodontitis tissues. The infiltration of different immune cell subtypes in the periodontitis site could lead the host immunity against periodontitis.

Sign in / Sign up

Export Citation Format

Share Document