scholarly journals Systemic Inflammation in Progressive Multiple Sclerosis Involves Follicular T-Helper, Th17- and Activated B-Cells and Correlates with Progression

PLoS ONE ◽  
2013 ◽  
Vol 8 (3) ◽  
pp. e57820 ◽  
Author(s):  
Jeppe Romme Christensen ◽  
Lars Börnsen ◽  
Rikke Ratzer ◽  
Fredrik Piehl ◽  
Mohsen Khademi ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
B Cells ◽  
Systemic Inflammation ◽  
Progressive Multiple Sclerosis ◽  
T Helper ◽  
Activated B Cells

scholarly journals Tolerogenicity of resting and activated B cells.

1994 ◽  
Vol 179 (1) ◽  
pp. 249-258 ◽  
Author(s):  
K M Gilbert ◽  
W O Weigle
Keyword(s):  
B Cells ◽  
Primary Cultures ◽  
Th1 Cells ◽  
T Helper ◽  
T Helper 1 ◽  
Th1 Cell ◽  
Histocompatibility Complex ◽  
Human Gamma Globulin ◽  
Antigen Presenting ◽  
Activated B Cells

Antigen presentation by resting splenic B cells has been shown previously to induce T helper 1 cell (Th1) anergy. In contrast to expectations, it was found here that B cells treated with F(ab')2 goat anti-mouse immunoglobulin (IgM) for 24 or 48 h also presented antigen (Ag) to Th1 cells in a manner that induced dramatic Ag-specific proliferative inactivation. The tolerogenicity of the anti-Ig-treated B cells was consistent with the observation that these B cells were only slightly more efficient than resting B cells in stimulating human gamma globulin (HGG)-induced proliferation of HGG-specific Th1 cells in primary cultures. The activated B cells were, however, more efficient than resting B cells in stimulating a primary mixed leukocyte reaction, and exhibited increased expression of major histocompatibility complex class II molecules, RL388 Ag and transferrin receptor. In addition, unlike resting B cells, which expressed little detectable B7, anti-Ig-treated B cells expressed high levels of B7. The functional capacity of the B7 expressed on the activated B cells was demonstrated by the fact that the Ag-presenting capacity of these B cells was inhibited by the addition to culture of CTLA4Ig, a soluble receptor for B7. It is unlikely that the tolerogenicity of the activated B cells was due to an inability of the Th1 cells to respond to B7 signals; the Th1 clones used in the experiments, unlike the Th2 clones tested, expressed CD28, the ligand for B7. In addition, anti-CD28 monoclonal antibody inhibited the induction of Th1 cell anergy when added to cultures of Th1 cells and Ag-pulsed fixed antigen-presenting cells. Taken together, the results indicate that B cells, even when activated, do not satisfy the costimulatory requirements of the Th1 cells used here, and therefore can present Ag in a tolerogenic fashion to Th1 cells. The costimulator deficiency of activated B cells may reflect an inadequacy in the level of B7 expressed or a lack of some other molecule.

Cyclophosphamide modulates CD4+ T cells into a T helper type 2 phenotype and reverses increased IFN-γ production of CD8+ T cells in secondary progressive multiple sclerosis

2004 ◽  
Vol 146 (1-2) ◽  
pp. 189-198 ◽  
Author(s):  
Arnon Karni ◽  
Konstantin Balashov ◽  
Wayne W. Hancock ◽  
Padmanabhan Bharanidharan ◽  
Michal Abraham ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
T Cells ◽  
Cd8 T Cells ◽  
Cd4 T Cells ◽  
Progressive Multiple Sclerosis ◽  
T Helper ◽  
Secondary Progressive ◽  
Ifn Γ ◽  
Helper Type

scholarly journals Activated B cells express receptors for, and proliferate in response to, pure interleukin 2.

1984 ◽  
Vol 160 (4) ◽  
pp. 1170-1183 ◽  
Author(s):  
R H Zubler ◽  
J W Lowenthal ◽  
F Erard ◽  
N Hashimoto ◽  
R Devos ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
T Cells ◽  
B Cells ◽  
B Cell ◽  
Interleukin 2 ◽  
T Helper ◽  
Spleen Cells ◽  
Human Spleen ◽  
Apparent Dissociation Constant ◽  
Activated B Cells

In this study we investigated whether interleukin 2 (IL-2) acts on B cell proliferation and whether activated B cells express IL-2 receptors. First, the functional activity of immunoaffinity-purified or recombinant human IL-2 was studied in a B blast assay using positively selected murine surface Ig-positive cells that had been activated by lipopolysaccharide (LPS) plus anti-Ig antibodies (anti-Ig). In this assay, T cells were not detected by fluorescence-activated cell sorter analysis. It was found that both IL-2 preparations led to optimal B cell proliferation compared with supernatants obtained from murine or human spleen cells or murine cloned T helper cells. Second, we observed that the IL-2 requirement in this assay was about the same as in a proliferation assay using lectin-activated polyclonal murine Lyt-2-positive T cells. Third, analysis of the binding of radiolabeled immunoaffinity-purified IL-2 to B cells indicated that LPS plus anti-Ig-activated B cells expressed a mean of 3,500 IL-2 receptors per cell with an apparent dissociation constant of 150 pM. However, neither nonactivated B cells nor B cells activated by LPS alone exhibited significant specific IL-2 binding. The functional and the receptor data are consistent with the conclusion that IL-2 is a growth factor not only for T cells but also for B cells.

scholarly journals Transcribed B lymphocyte genes and multiple sclerosis risk genes are underrepresented in Epstein–Barr Virus hypomethylated regions

2019 ◽  
Vol 21 (2) ◽  
pp. 91-99 ◽  
Author(s):  
Lawrence T. C. Ong ◽  
Grant P. Parnell ◽  
Ali Afrasiabi ◽  
Graeme J. Stewart ◽  
Sanjay Swaminathan ◽  
...  
Keyword(s):  
Gene Expression ◽  
Multiple Sclerosis ◽  
B Cells ◽  
Epstein Barr Virus ◽  
B Lymphocyte ◽  
Sequencing Data ◽  
Barr Virus ◽  
Ebv Infection ◽  
Epstein Barr ◽  
Activated B Cells

Abstract Epstein–Barr Virus (EBV) infection appears to be necessary for the development of Multiple Sclerosis (MS), although the specific mechanisms are unknown. More than 200 single-nucleotide polymorphisms (SNPs) are known to be associated with the risk of developing MS. About a quarter of these are also highly associated with proximal gene expression in B cells infected with EBV (lymphoblastoid cell lines—LCLs). The DNA of LCLs is hypomethylated compared with both uninfected and activated B cells. Since methylation can affect gene expression, and so cell differentiation and immune evasion, we hypothesised that EBV-driven hypomethylation may affect the interaction between EBV infection and MS. We interrogated an existing dataset comprising three individuals with whole-genome bisulfite sequencing data from EBV transformed B cells and CD40L-activated B cells. DNA methylation surrounding MS risk SNPs associated with gene expression in LCLs (LCLeQTL) was less likely to be hypomethylated than randomly selected chromosomal regions. Differential methylation was independent of genomic features such as promoter regions, but genes preferentially expressed in EBV-infected B cells, including the LCLeQTL genes, were underrepresented in the hypomethylated regions. Our data does not indicate MS genetic risk is affected by EBV hypomethylation.

scholarly journals The Role of B Cells in Primary Progressive Multiple Sclerosis

2021 ◽  
Vol 12 ◽  
Author(s):  
Jameson P. Holloman ◽  
Robert C. Axtell ◽  
Nancy L. Monson ◽  
Gregory F. Wu
Keyword(s):  
Multiple Sclerosis ◽  
Cell Differentiation ◽  
T Cell ◽  
B Cells ◽  
B Cell ◽  
Cytokine Production ◽  
Progressive Multiple Sclerosis ◽  
T Cell Differentiation ◽  
Primary Progressive Multiple Sclerosis ◽  
Antibody Synthesis

The success of ocrelizumab in reducing confirmed disability accumulation in primary progressive multiple sclerosis (PPMS) via CD20-targeted depletion implicates B cells as causal agents in the pathogenesis of PPMS. This review explores the possible mechanisms by which B cells contribute to disease progression in PPMS, specifically exploring cytokine production, antigen presentation, and antibody synthesis. B cells may contribute to disease progression in PPMS through cytokine production, specifically GM-CSF and IL-6, which can drive naïve T-cell differentiation into pro-inflammatory Th1/Th17 cells. B cell production of the cytokine LT-α may induce follicular dendritic cell production of CXCL13 and lead indirectly to T and B cell infiltration into the CNS. In contrast, production of IL-10 by B cells likely induces an anti-inflammatory effect that may play a role in reducing neuroinflammation in PPMS. Therefore, reduced production of IL-10 may contribute to disease worsening. B cells are also capable of potent antigen presentation and may induce pro-inflammatory T-cell differentiation via cognate interactions. B cells may also contribute to disease activity via antibody synthesis, although it's unlikely the benefit of ocrelizumab in PPMS occurs via antibody decrement. Finally, various B cell subsets likely promulgate pro- or anti-inflammatory effects in MS.

scholarly journals Emerging Role of Follicular T Helper Cells in Multiple Sclerosis and Experimental Autoimmune Encephalomyelitis

2018 ◽  
Author(s):  
James Quinn ◽  
Robert Axtell
Keyword(s):  
Multiple Sclerosis ◽  
B Cells ◽  
Autoimmune Disorder ◽  
T Helper ◽  
Autoimmune Encephalomyelitis ◽  
Ample Evidence ◽  
Tfh Cells ◽  
Follicular T Helper Cells ◽  
Experimental Autoimmune

Multiple sclerosis is an autoimmune disorder where both T cells and B cells are implicated in pathology. However, it remains unclear how these two distinct populations cooperate to drive disease. There is ample evidence from studies in both MS patients and mouse models that Th17, B cells, and follicular T helper (TFH) cells contribute to disease. This review article describes the literature that identifies mechanisms by which Th17, TFH, and B cells cooperatively drive disease activity in MS and EAE. The curation of this literature has identified that CNS-infiltrating TFH cells act with TH17 cell to contribute to an inflammatory B cell response in neuroinflammation. This demonstrates that TFH cells and their products are promising targets for therapies in MS.

Sign in / Sign up

Export Citation Format

Share Document