scholarly journals Vitamin D3 Suppresses Class II Invariant Chain Peptide Expression on Activated B-Lymphocytes: A Plausible Mechanism for Downregulation of Acute Inflammatory Conditions

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Omar K. Danner ◽  
Leslie R. Matthews ◽  
Sharon Francis ◽  
Veena N. Rao ◽  
Cassie P. Harvey ◽  
...  
Keyword(s):  
B Cell ◽  
B Lymphocytes ◽  
Vitamin D3 ◽  
Cell Function ◽  
Ex Vivo ◽  
Class Ii ◽  
Invariant Chain ◽  
Ex Vivo Model ◽  
Fluorescent Intensity ◽  
Inflammatory Conditions

Class II invariant chain peptide (CLIP) expression has been demonstrated to play a pivotal role in the regulation of B cell function after nonspecific polyclonal expansion. Several studies have shown vitamin D3 helps regulate the immune response. We hypothesized that activated vitamin D3 suppresses CLIP expression on activated B-cells after nonspecific activation or priming of C57BL/6 mice with CpG. This study showed activated vitamin D3 actively reduced CLIP expression and decreased the number of CLIP+B-lymphocytes in a dose and formulation dependent fashion. Flow cytometry was used to analyze changes in mean fluorescent intensity (MFI) based on changes in concentration of CLIP on activated B-lymphocytes after treatment with the various formulations of vitamin D3. The human formulation of activated vitamin D (calcitriol) had the most dramatic reduction in CLIP density at an MFI of 257.3 [baseline of 701.1 (Pvalue = 0.01)]. Cholecalciferol and alfacalcidiol had no significant reduction in MFI at 667.7 and 743.0, respectively. Calcitriol seemed to best reduce CLIP overexpression in this ex vivo model. Bioactive vitamin D3 may be an effective compliment to other B cell suppression therapeutics to augment downregulation of nonspecific inflammation associated with many autoimmune disorders. Further study is necessary to confirm these findings.

scholarly journals Both IFN-γ and IL-4 Induce MHC Class II Expression at the Surface of Mouse Pro-B Cells

1997 ◽  
Vol 5 (2) ◽  
pp. 115-120 ◽  
Author(s):  
Suzanne Lombard-Platet ◽  
Valerie Meyer ◽  
Rhodri Ceredig
Keyword(s):  
B Cells ◽  
B Cell ◽  
Mhc Class Ii ◽  
Class Ii ◽  
Invariant Chain ◽  
B Cell Differentiation ◽  
Cell Clones ◽  
Ifn Γ ◽  
B Lymphoid ◽  
Mhc Class Ii Molecules

Pro-B cells are early B-cell progenitors that retain macrophage potential. We have studied MHC class II molecules and invariant chain inducibility on four class II negative mouse pro- B-cell clones. We analyzed the effects of IL-4 and IFN-γ, which represent the major inducers of class II in the B-lymphoid and monocytic/macrophage lineages, respectively. After 48 h of treatment with either cytokine, three pro-B-cell clones (C2.13, A1.5, and F2.2) expressed intracellular invariant chain and cell-surface class II molecules. One clone (D2.1) remained negative. As already reported, more differentiated 70Z/3 pre-B cells were inducible by IL-4 only. These data suggest that the induction of class II and invariant-chain genes are subject to regulation throughout B-cell differentiation.

scholarly journals Immunoglobulin secretory function of B cells from untreated patients with chronic lymphocytic leukemia and hypogammaglobulinemia: role of T cells

Blood ◽  
1983 ◽  
Vol 62 (4) ◽  
pp. 767-774 ◽  
Author(s):  
LA Fernandez ◽  
JM MacSween ◽  
GR Langley
Keyword(s):  
T Cells ◽  
B Cells ◽  
Chronic Lymphocytic Leukemia ◽  
B Cell ◽  
B Lymphocytes ◽  
Peripheral Blood ◽  
Cell Function ◽  
Lymphocytic Leukemia ◽  
Suppressor Activity ◽  
Normal Peripheral Blood

Abstract The mechanism of the hypogammaglobulinemia in patients with chronic lymphocytic leukemia (CLL) was studied by determining the generation of specific immunoglobulin-secreting cells in response to mitogen and antigen stimulation in culture. Normal peripheral blood B lymphocytes from 18 normal subjects cocultured with equal numbers of autologous T cells generated cells secreting 2,542 +/- 695 IgG, 2,153 +/- 615 IgA, and 2,918 +/- 945 IgM. Normal B lymphocytes cocultured with normal allogeneic T cells generated similar numbers. However, B lymphocytes from patients with chronic lymphocytic leukemia cocultured with T cells from the same patient generated only 0.5% as many cells secreting IgG and 11% and 23% as many secreting IgA and IgM, respectively. The reason for this markedly defective generation of immunoglobulin-secreting cells was investigated by evaluating T-helper, T-suppressor, and B-cell function using B cells from tonsil and T and B cells from peripheral blood of normal and leukemic individuals. T cells from patients with chronic lymphocytic leukemia provided somewhat greater help than did normal T cells to normal peripheral blood B cells and normal help to tonsil B cells, whether stimulated with mitogen or antigen. T cells from patients with chronic lymphocytic leukemia did not demonstrate increased suppressor function compared to normals with B cells from normal peripheral blood. The hypogammaglobulinemia in these patients therefore was associated with a markedly defective generation of immunoglobulin secreting cells, and as there was normal or increased T- cell helper activity without excessive suppressor activity, it seems likely that this was due to an intrinsic B-cell defect.

scholarly journals Inflammatory Conditions Dictate the Effect of Mesenchymal Stem or Stromal Cells on B Cell Function

2017 ◽  
Vol 8 ◽  
Author(s):  
Franka Luk ◽  
Laura Carreras-Planella ◽  
Sander S. Korevaar ◽  
Samantha F. H. de Witte ◽  
Francesc E. Borràs ◽  
...  
Keyword(s):  
B Cell ◽  
Stromal Cells ◽  
Cell Function ◽  
B Cell Function ◽  
Inflammatory Conditions

scholarly journals Cell-Specific Association and Shuttling of IκBα Provides a Mechanism for Nuclear NF-κB in B Lymphocytes

2001 ◽  
Vol 21 (14) ◽  
pp. 4837-4846 ◽  
Author(s):  
Winnie F. Tam ◽  
Weihong Wang ◽  
Ranjan Sen
Keyword(s):  
B Cell ◽  
B Lymphocytes ◽  
Nuclear Import ◽  
Nuclear Export ◽  
Cell Function ◽  
Subunit Composition ◽  
Mouse Strains ◽  
B Cell Function ◽  
Cell Specificity ◽  
Specific Association

ABSTRACT Mature B lymphocytes are unique in containing nuclear Rel proteins prior to cell stimulation. This activity consists largely of p50–c-Rel heterodimers, and its importance for B-cell function is exemplified by reduced B-cell viability in several genetically altered mouse strains. Here we suggest a mechanism for the cell specificity and the subunit composition of constitutive B-cell NF-κB based on the observed properties of Rel homo- and heterodimers and IκBα. We show that c-Rel lacks a nuclear export sequence, making the removal of c-Rel-containing complexes from the nucleus less efficient than removal of p65-containing complexes. Second, the nuclear import potential of p65 and c-Rel homodimers but not p50-associated heterodimers was attenuated when they were complexed to IκBα, leading to a greater propensity of heterodimers to be nuclear. We propose that subunit composition of B-cell NF-κB reflects the inefficient retrieval of p50–c-Rel heterodimers from the nucleus. Cell specificity may be a consequence of c-Rel–IκBα complexes being present only in mature B cells, which leads to nuclear c-Rel due to IκBα turnover and shuttling of the complex.

scholarly journals B lymphocytes undergo TLR2-dependent apoptosis upon Shigella infection

2014 ◽  
Vol 211 (6) ◽  
pp. 1215-1229 ◽  
Author(s):  
Katharina Nothelfer ◽  
Ellen T. Arena ◽  
Laurie Pinaud ◽  
Michel Neunlist ◽  
Brian Mozeleski ◽  
...  
Keyword(s):  
Cell Death ◽  
B Cell ◽  
B Lymphocytes ◽  
B Lymphocyte ◽  
Ex Vivo ◽  
Functionally Impaired ◽  
Rectal Biopsies ◽  
Type Three Secretion

Antibody-mediated immunity to Shigella, the causative agent of bacillary dysentery, requires several episodes of infection to get primed and is short-lasting, suggesting that the B cell response is functionally impaired. We show that upon ex vivo infection of human colonic tissue, invasive S. flexneri interacts with and occasionally invades B lymphocytes. The induction of a type three secretion apparatus (T3SA)–dependent B cell death is observed in the human CL-01 B cell line in vitro, as well as in mouse B lymphocytes in vivo. In addition to cell death occurring in Shigella-invaded CL-01 B lymphocytes, we provide evidence that the T3SA needle tip protein IpaD can induce cell death in noninvaded cells. IpaD binds to and induces B cell apoptosis via TLR2, a signaling receptor thus far considered to result in activation of B lymphocytes. The presence of bacterial co-signals is required to sensitize B cells to apoptosis and to up-regulate tlr2, thus enhancing IpaD binding. Apoptotic B lymphocytes in contact with Shigella-IpaD are detected in rectal biopsies of infected individuals. This study therefore adds direct B lymphocyte targeting to the diversity of mechanisms used by Shigella to dampen the host immune response.

Inflammatory conditions dictate the effect of mesenchymal stem cells on B cell function

Cytotherapy ◽  
2017 ◽  
Vol 19 (5) ◽  
pp. S39-S40
Author(s):  
F. Luk ◽  
L. Carreras-Planella ◽  
S. Korevaar ◽  
S.F. de Witte ◽  
F.E. Borràs ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
B Cell ◽  
Cell Function ◽  
B Cell Function ◽  
Inflammatory Conditions

scholarly journals Temporal multiomic modeling reveals a B-cell receptor proliferative program in chronic lymphocytic leukemia

Leukemia ◽  
2021 ◽  
Author(s):  
Cedric Schleiss ◽  
Raphael Carapito ◽  
Luc-Matthieu Fornecker ◽  
Leslie Muller ◽  
Nicodème Paul ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
B Cell ◽  
Cellular Response ◽  
Ex Vivo ◽  
Cell Receptor ◽  
B Cell Receptor ◽  
Lymphocytic Leukemia ◽  
Leukemic Cells ◽  
Ex Vivo Model ◽  
Innovative Therapy

AbstractB-cell receptor (BCR) signaling is crucial for the pathophysiology of most mature B-cell lymphomas/leukemias and has emerged as a therapeutic target whose effectiveness remains limited by the occurrence of mutations. Therefore, deciphering the cellular program activated downstream this pathway has become of paramount importance for the development of innovative therapies. Using an original ex vivo model of BCR-induced proliferation of chronic lymphocytic leukemia cells, we generated 108 temporal transcriptional and proteomic profiles from 1 h up to 4 days after BCR activation. This dataset revealed a structured temporal response composed of 13,065 transcripts and 4027 proteins, comprising a leukemic proliferative signature consisting of 430 genes and 374 proteins. Mathematical modeling of this complex cellular response further highlighted a transcriptional network driven by 14 early genes linked to proteins involved in cell proliferation. This group includes expected genes (EGR1/2, NF-kB) and genes involved in NF-kB signaling modulation (TANK, ROHF) and immune evasion (KMO, IL4I1) that have not yet been associated with leukemic cells proliferation. Our study unveils the BCR-activated proliferative genetic program in primary leukemic cells. This approach combining temporal measurements with modeling allows identifying new putative targets for innovative therapy of lymphoid malignancies and also cancers dependent on ligand–receptor interactions.

scholarly journals Evaluation of phagocytic cell function in an ex vivo model of hemodialysis

1990 ◽  
Vol 37 (2) ◽  
pp. 776-782 ◽  
Author(s):  
Richard A. Ward ◽  
Bärbel Schmidt ◽  
Matthias Blumenstein ◽  
Hans J. Gurland
Keyword(s):  
Cell Function ◽  
Ex Vivo ◽  
Phagocytic Cell ◽  
Ex Vivo Model ◽  
Phagocytic Cell Function

Integrin-associated protein/CD47 regulates motile activity in human B-cell lines through CDC42

Blood ◽  
2000 ◽  
Vol 96 (1) ◽  
pp. 234-241 ◽  
Author(s):  
Hitoshi Yoshida ◽  
Yoshiaki Tomiyama ◽  
Jun Ishikawa ◽  
Kenji Oritani ◽  
Itaru Matsumura ◽  
...  
Keyword(s):  
Cell Migration ◽  
B Cell ◽  
B Lymphocytes ◽  
Cell Lines ◽  
Cell Function ◽  
Dominant Negative ◽  
Migratory Activity ◽  
Functional Changes ◽  
Dominant Negative Form ◽  
Negative Form

Cell migration requires a dynamic interaction between the cell, its substrate, and the cytoskeleton-associated motile apparatus. Integrin-associated protein (IAP)/CD47 is a 50-kd cell surface protein that is physically associated with β3 integrins and that modulates the functions of β3 integrins in various cells. However, in B-lymphocytes that express β1 integrins but few β3 integrins, the roles of IAP/CD47 remain to be determined. Cross-linking of IAP/CD47 by the immobilized anti-IAP/CD47 monoclonal antibody (mAb) B6H12, but not 2D3, produced signals to promote polarization with lamellipodia, a characteristic morphology during leukocyte migration, in pre-B and mature B-cell lines (BALL, Nalm6, ONHL-1, Daudi), but not in myeloma cell lines (RPMI8226, OPM-2). In the presence of the immobilized fibronectin (FN), soluble B6H12 could increase the rate of the polarization and activate migratory activity of BALL cells to FN in a transwell filter assay. Furthermore, the dominant-negative form of CDC42 completely blocked B6H12-induced morphologic and functional changes without inhibiting phorbol 12-myristate 13-acetate–induced spreading on FN in BALL cells, whereas the dominant-negative form of Rac1 inhibited all these changes. These findings demonstrate that in B-lymphocytes, IAP/CD47 may transduce the signals to activate the migratory activity, in which CDC42 may be specifically involved, and that IAP/CD47 shows synergistic effect with 4β1 on B-cell migration. These findings would provide new insight into the role of IAP/CD47 on B-cell function.

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