scholarly journals Innate-like self-reactive B cells infiltrate human renal allografts during transplant rejection

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Yuta Asano ◽  
Joe Daccache ◽  
Dharmendra Jain ◽  
Kichul Ko ◽  
Andrew Kinloch ◽  
...  
Keyword(s):  
B Cells ◽  
Plasma Cells ◽  
Transplant Rejection ◽  
Transplant Recipients ◽  
Tissue Destruction ◽  
Renal Allografts ◽  
Cell Proliferation And Differentiation ◽  
Proliferation And Differentiation ◽  
Specific Antigens ◽  
Transcriptional State

AbstractIntrarenal B cells in human renal allografts indicate transplant recipients with a poor prognosis, but how these cells contribute to rejection is unclear. Here we show using single-cell RNA sequencing that intrarenal class-switched B cells have an innate cell transcriptional state resembling mouse peritoneal B1 or B-innate (Bin) cells. Antibodies generated by Bin cells do not bind donor-specific antigens nor are they enriched for reactivity to ubiquitously expressed self-antigens. Rather, Bin cells frequently express antibodies reactive with either renal-specific or inflammation-associated antigens. Furthermore, local antigens can drive Bin cell proliferation and differentiation into plasma cells expressing self-reactive antibodies. These data show a mechanism of human inflammation in which a breach in organ-restricted tolerance by infiltrating innate-like B cells drives local tissue destruction.

scholarly journals Intrarenal B cells integrate in situ innate and adaptive immunity in human renal allograft rejection

2020 ◽  
Author(s):  
Yuta Asano ◽  
Joe Daccache ◽  
Dharmendra Jain ◽  
Kichul Ko ◽  
Andrew Kinloch ◽  
...  
Keyword(s):  
B Cells ◽  
Allograft Rejection ◽  
Renal Allograft ◽  
Plasma Cells ◽  
Tissue Destruction ◽  
Cell Proliferation And Differentiation ◽  
Proliferation And Differentiation ◽  
Specific Antigens ◽  
B1 Cells

AbstractIn human allograft rejection, intrarenal B cell infiltrates identify those with a poor prognosis. However, how intrarenal B cells contribute to rejection is not known. Single cell RNA-sequencing of intrarenal class-switched B cells revealed a unique innate cell transcriptional state resembling murine peritoneal B1 cells (Bin cells). Comparison to the transcriptome of whole renal allograft rejecting tissue revealed that Bin cells existed within a complex autocrine and paracrine network of signaling axes. The immunoglobulins expressed by Bin cells did not bind donor specific antigens nor were they enriched for reactivity to ubiquitously expressed self-antigens. Rather, Bin cells frequently expressed antibodies reactive with renal expressed antigens. Furthermore, local antigens could drive Bin cell proliferation and differentiation into plasma cells expressing self-reactive antibodies. By contributing to local innate immune networks, and expressing antibodies reactive with renal expressed antigens, Bin cells are predicted to amplify local inflammation and tissue destruction.

scholarly journals Follicular Helper T Cell Derived Exosomes Promote B Cell Proliferation and Differentiation in Antibody-Mediated Rejection after Renal Transplantation

2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Jintao Yang ◽  
Lili Bi ◽  
Xiuyun He ◽  
Zhen Wang ◽  
Yeyong Qian ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Renal Transplantation ◽  
B Cells ◽  
B Cell ◽  
Magnetic Beads ◽  
Plasma Cells ◽  
Antibody Mediated Rejection ◽  
Follicular Helper ◽  
Cell Proliferation And Differentiation ◽  
Proliferation And Differentiation

Follicular helper T cells (Tfh cells) are closely related to the occurrence and development of antibody-mediated rejection (AMR) after renal transplantation. Exosomes play a key role in the rejection after organ transplantation. However, whether Tfh-derived exosomes are involved in AMR has not been reported. We collected peripheral blood from 42 kidney transplant patients and found no significant differences in CD4+CXCR5+ and CD4+CXCR5+CXCR3+CCR6-exosomes between AMR and non-AMR groups, whereas the proportion of CD4+CXCR5+CXCR3-exosomes was significantly higher in AMR group than that in non-AMR group; CTLA-4 expression of CD4+CXCR5+exosomes was significantly lower in AMR group than that in non-AMR group. HLA-G expression was not significantly different between two groups. We further separated CD4+CXCR5+cells from patients by magnetic beads. Coculture experiments showed that Tfh cell-derived exosomes in AMR patients significantly promoted B cell proliferation and differentiation, compared with non-AMR group, the percentage of B cells and plasma cells increased by 87.52% and 110.2%, respectively. In conclusion, our study found that Tfh cell-derived exosomes could promote the proliferation and differentiation of B cells and they may play an important role in the development of AMR after renal transplantation.

Vitamin A potentiates CpG-mediated memory B-cell proliferation and differentiation: involvement of early activation of p38MAPK

Blood ◽  
2007 ◽  
Vol 109 (9) ◽  
pp. 3865-3872 ◽  
Author(s):  
Aase Ertesvag ◽  
Hans-Christian Aasheim ◽  
Soheil Naderi ◽  
Heidi Kiil Blomhoff
Keyword(s):  
B Cells ◽  
Humoral Immunity ◽  
Plasma Cells ◽  
Cell Formation ◽  
Memory B Cells ◽  
Cyclin D3 ◽  
Human B Cells ◽  
Cell Proliferation And Differentiation ◽  
Proliferation And Differentiation ◽  
Enhanced Expression

Abstract Foreign CpG-DNA from viruses and bacteria can activate memory B cells through binding to toll-like receptor 9, and this pathway has been hypothesized to be involved in the continuous activation of memory B cells ensuring life-long humoral immunity. In this study, we demonstrate that retinoic acid (RA) is a potent coactivator of this pathway in human B cells. RA enhanced the CpG-mediated proliferation of CD27+ memory B cells, and the proliferative response was accompanied by increased immunoglobulin (Ig) secretion indicative of plasma-cell formation. The RA-induced proliferation was preceded by enhanced expression of cyclin D3, and both the expression of cyclin D3 and the induced Ig secretion were found to be dependent on IL-10. Of importance, RA increased the CpG-induced phosphorylation of ERK1/2, p38MAPK, and IκB as early as 30 minutes after stimulation. By using specific inhibitors, all the RA-mediated events, including proliferation, cyclin D3 expression, IL-10 secretion, and Ig secretion, were shown to be dependent on p38MAPK. Hence, we propose that RA can strengthen humoral immunity by promoting CpG-mediated stimulation of CD27+ B cells via activation of p38MAPK resulting in increased proliferation and differentiation to Ig-secreting plasma cells.

scholarly journals The staphylococcal toxic shock syndrome toxin 1 triggers B cell proliferation and differentiation via major histocompatibility complex-unrestricted cognate T/B cell interaction.

1989 ◽  
Vol 170 (6) ◽  
pp. 2011-2022 ◽  
Author(s):  
W Mourad ◽  
P Scholl ◽  
A Diaz ◽  
R Geha ◽  
T Chatila
Keyword(s):  
Cell Proliferation ◽  
B Cells ◽  
B Cell ◽  
Mhc Class Ii ◽  
Cell Interaction ◽  
Class Ii ◽  
Toxic Shock ◽  
Cell Proliferation And Differentiation ◽  
Proliferation And Differentiation ◽  
Toxic Shock Syndrome Toxin

The Staphylococcus aureus exotoxin toxic shock syndrome toxin 1 (TSST-1) is a potent activator of T cells and monocytes. We have recently demonstrated that TSST-1 is a superantigen that binds monomorphic determinants on MHC class II molecules. In the present study, we have examined the effect of TSST-1 on the activation and differentiation of high density human tonsillar B cells. TSST-1 bound to tonsilar B cells with high affinity and saturation kinetics. This binding was effectively inhibited by a combination of anti-HLA-DR and anti-HLA-DQ mAbs. Treatment of purified B cells with TSST-1 failed to induce B cell proliferation or Ig production. However, in the presence of irradiated T cells, TSST-1 induced resting B cells to proliferate and differentiate into Ig secretory cells. TSST-1 mimicked nominal antigen in that its induction of B cell responses was strictly dependent on physical contact between T and B cells, and was profoundly inhibited by anti-MHC class II mAbs, anti-CD3 mAbs, and, to a lesser extent, by anti-CD18 mAbs. However, unlike nominal antigen, TSST-1-mediated T/B cell interactions were MHC unrestricted. These results suggest that TSST-1 induces T cell-dependent B cell proliferation and differentiation by virtue of its ability to mediate MHC-unrestricted cognate T/B cell interaction via the TCR/CD3 complex and MHC class II antigens.

scholarly journals Interleukin 10 (IL-10) upregulates functional high affinity IL-2 receptors on normal and leukemic B lymphocytes.

1993 ◽  
Vol 178 (5) ◽  
pp. 1473-1481 ◽  
Author(s):  
A C Fluckiger ◽  
P Garrone ◽  
I Durand ◽  
J P Galizzi ◽  
J Banchereau
Keyword(s):  
B Cells ◽  
B Cell ◽  
B Lymphocytes ◽  
Flow Cytometric Analysis ◽  
Interleukin 10 ◽  
Lymphocytic Leukemia ◽  
High Affinity ◽  
Cell Proliferation And Differentiation ◽  
Proliferation And Differentiation ◽  
High Affinity Receptor

Interleukin 10 (IL-10) has recently been shown to induce normal human B lymphocytes to proliferate and differentiate into immunoglobulin (Ig)-secreting cells. Herein, we show that IL-10 also promotes DNA synthesis and IgM production by anti-CD40 activated B cell chronic lymphocytic leukemia (B-CLL). Most strikingly, IL-2 and IL-10 were found to synergize to induce the proliferation and differentiation of B-CLL cells. This synergy between IL-2 and IL-10 was also observed with normal B cells which proliferated strongly and secreted large amounts of IgM, IgG, and IgA. The observed synergy is likely to be due to the IL-10-induced increase of high affinity IL-2 receptors on both normal and leukemic B cells. This increase of high affinity receptor is associated to an increase of Tac/CD25 expression that can be detected by flow cytometric analysis. Taken together, these results indicate that IL-10 permits anti-CD40 activated B cells to respond to IL-2 through an induction of high affinity IL-2 receptors. This effect of IL-10 may partly explain how T cells, which activate B cells in a CD40-dependent fashion, induce B cell proliferation and differentiation mostly through IL-2.

scholarly journals Elevated number of IL-21+ TFH and CD86+CD38+ B cells in blood of renal transplant recipients with AMR under conventional immuno-suppression

2022 ◽  
Vol 36 ◽  
pp. 205873842110480
Author(s):  
Jing Liu ◽  
Tongyu Tang ◽  
Zhihui Qu ◽  
Li Wang ◽  
Rui Si ◽  
...  
Keyword(s):  
B Cells ◽  
Renal Transplant ◽  
Acute Rejection ◽  
Plasma Cells ◽  
Renal Transplant Recipients ◽  
Transplant Recipients ◽  
Post Transplantation ◽  
Tfh Cells ◽  
Stage Renal Disease ◽  
End Stage

The objective of this study is to detect the number of different subsets of TFH and B cells in renal transplant recipients (RTR) with antibody-mediated acute rejection (AMR), acute rejection (AR), chronic rejection (CR), or transplant stable (TS). The present study was a prospective study. The numbers of ICOS +, PD-1+ and IL-21+ TFH, CD86+, CD38+, CD27+, and IgD- B cells in 21 patients with end-stage renal disease (ESRD) and post-transplant times were measured by flow cytometry. The level of serum IL-21 was detected by ELISA. The numbers of circulating CD4+CXCR5+, CD4+CXCR5+ICOS+, CD4+CXCR5+PD-1+, CD4+CXCR5+IL-21+ TFH, CD19+CD86+, and CD19 +CD86+CD38+ B cells as well as the level of serum IL-21 in the AMR, AR, and CR groups at post-transplantation were significantly higher than those at pre-transplantation. In contrast, the number of circulating CD19+CD27+IgD B cells was significantly increased in the TS groups in respect to the other groups. Moreover, the numbers of circulating CD4+CXCR5+IL-21+ TFH cells, CD19+CD86+CD38+ B cells as well as the level of serum IL-21 were positive related to the level of serum Cr while showing negative correlated with the values of eGFR in the AMR groups at post-transplantation for 4 and 12 weeks. Circulating TFH cells may be a biomarker in RTR with AMR, which can promote the differentiation of B cells into plasma cells by activating B cells, thereby promoting disease progression.

scholarly journals Therapeutic Antibodies and Cancer Vaccines

2019 ◽  
Author(s):  
Mahnoor Patel
Keyword(s):  
B Cells ◽  
Tumor Antigens ◽  
Plasma Cells ◽  
Therapeutic Vaccine ◽  
The Body ◽  
Therapeutic Antibodies ◽  
Virus Infections ◽  
Natural Defense ◽  
Proliferation And Differentiation ◽  
Anticancer Vaccines

Antibodies are proteins synthesized in blood against specific antigens. Antigen binding causes activation, proliferation and differentiation of the B cells. After activation, B cells becomes plasma cells and secrete antibodies. Therapeutic antibodies are monoclonal antibodies and use as passive immunotherapy for the treatment of cancer. It is well established option in clinical oncology. Anticancer vaccines are less advanced because of some exception of successfully applied prophylactic vaccines against oncogenic virus infections. The formation of therapeutic vaccine is still a great challenge due to the self nature of tumor antigens. Therapeutic antibodies as vaccines against cancer are produced in healthy cells by using cancer antigens and use for the patient to treat existing cancer by strengthening the natural defense of the body against cancer.

scholarly journals Targeting B Cells and Plasma Cells in Glomerular Diseases: Translational Perspectives

2018 ◽  
Vol 29 (3) ◽  
pp. 741-758 ◽  
Author(s):  
Eva Schrezenmeier ◽  
David Jayne ◽  
Thomas Dörner
Keyword(s):  
B Cells ◽  
Plasma Cells ◽  
Kidney Diseases ◽  
Transplant Rejection ◽  
Proteasome Inhibition ◽  
Memory B Cells ◽  
Glomerular Diseases ◽  
Targeted Interventions ◽  
Anca Associated Vasculitis ◽  
B Lineage

The unique contributions of memory B cells and plasma cells in kidney diseases remain unclear. In this review, we evaluate the clinical experience with treatments directed at B cells, such as rituximab, and at plasma cells, such as proteasome inhibition, to shed light on the role of these two B lineage compartments in glomerular diseases. Specifically, analysis of these targeted interventions in diseases such as ANCA-associated vasculitis, SLE, and antibody-mediated transplant rejection permits insight into the pathogenetic effect of these cells. Notwithstanding the limitations of preclinical models and clinical studies (heterogeneous populations, among others), the data suggest that memory B and plasma cells represent two engines of autoimmunity, with variable involvement in these diseases. Whereas memory B cells and plasma cells appear to be key in ANCA-associated vasculitis and antibody-mediated transplant rejection, respectively, SLE seems likely to be driven by both autoimmune compartments. These conclusions have implications for the future development of targeted therapeutics in immune-mediated renal disease.

Are Thymus-Derived Lymphocytes (T Cells) Defective in the Nasopharyngeal and Palatine tonsils of Children?

1993 ◽  
Vol 109 (4) ◽  
pp. 693-700 ◽  
Author(s):  
Joel M. Bernstein ◽  
Gary A. Rich ◽  
Christine Odziemiec ◽  
Mark Ballow
Keyword(s):  
T Cells ◽  
B Cells ◽  
Plasma Cells ◽  
Chronic Sinusitis ◽  
Cell Maturation ◽  
Suppressor Activity ◽  
Turn On ◽  
B Cell Maturation ◽  
Specific Antigens ◽  
Recurrent Otitis Media

The present study was conducted to evaluate the response of adenoidal T cells and B cells in the production of immunoglobulins. There appears to be a consistent inability of adenoidal T cells to turn on B cells to mature into immunoglobulin-secreting plasma cells. This phenomenon did not appear to be due to suppressor activity of adenoidal T cells because T cells from other sources appeared to effectively result in adenoidal B cell maturation, even in the presence of adenoidal T cells. Both tonsils and adenoids appear to have defective IL-2 production, in response to both mitogens and specific antigens. It is hypothesized that a cytokine(s) may be released in adenoids that downregulate IL-2 production and result in immune suppression in the adenoids of children with recurrent otitis media and chronic sinusitis.

scholarly journals Reduced Energy Metabolism Impairs T Cell-Dependent B Cell Responses in Patients With Advanced HBV-Related Cirrhosis

2021 ◽  
Vol 12 ◽  
Author(s):  
Chunhong Huang ◽  
Junwei Shao ◽  
Congcong Lou ◽  
Fengtian Wu ◽  
Tiantian Ge ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
T Cell ◽  
B Cells ◽  
Energy Metabolism ◽  
B Cell ◽  
Plasma Cells ◽  
Mtor Pathway ◽  
Cell Responses ◽  
Proliferation And Differentiation ◽  
B Cell Responses

Background and AimsPatients with decompensated HBV-related liver cirrhosis (HBV D-LC) showed compromised immune responses, which manifested as a proneness to develop infections and hyporesponsiveness to vaccines, resulting in accelerated disease progression. The alterations in T cell-dependent B cell responses in this pathophysiological process were not well understood. This study aimed to investigate T cell-dependent B cell responses in this process and discuss the mechanism from the perspective of metabolism.MethodsChanges in phenotypes and subsets of peripheral B cells between HBV D-LC patients and healthy controls (HCs) were compared by flow cytometry. Isolated B cells were activated by coculture with circulating T follicular (cTfh) cells. After coculture, the frequencies of plasmablasts and plasma cells and immunoglobin levels were analyzed. Oxidative phosphorylation (OXPHOS) and glycolysis were analyzed by a Seahorse analyzer. Mitochondrial function and the AKT/mTOR pathway were analyzed by flow cytometry.ResultsThe proliferation and differentiation capacities of B cells after T cell stimulation were impaired in D-LC. Furthermore, we found that B cells from D-LC patients showed reductions in OXPHOS and glycolysis after activation, which may result from reduced glucose uptake, mitochondrial dysfunction and attenuated activation of the AKT/mTOR pathway.ConclusionsB cells from HBV D-LC patients showed dysfunctional energy metabolism after T cell-dependent activation. Understanding the regulations of B cell metabolic pathway and their changes may provide a new direction to rescue B cell hyporesponsiveness in patients with HBV D-LC, preventing these patients be infected and improving sensitivity to vaccines.

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