scholarly journals T cell regulation of B cell activation. Lyt-1+,2-T cells modify the MHC-restricted function of heterogeneous and cloned T suppressor cells.

1985 ◽  
Vol 162 (2) ◽  
pp. 413-426 ◽  
Author(s):  
Y Asano ◽  
R J Hodes
Keyword(s):  
T Cells ◽  
B Cells ◽  
Cell Activation ◽  
Cell Function ◽  
Suppressor Cells ◽  
Effector Function ◽  
B Cell Activation ◽  
Experimental Conditions ◽  
Th Cells ◽  
Mhc Restriction

Previous studies have shown the existence of both heterogeneous Lyt-1-,2+ suppressor (Ts) cells and cloned Lyt-1+,2- Ts cells which, despite the difference in their Lyt phenotypes, functioned in a similar antigen-specific and major histocompatibility complex (MHC)-restricted fashion to suppress the antibody responses generated by cloned helper T (Th) cells and hapten-primed B cells. Our studies were carried out to assess in further detail the genetically restricted cell interactions that mediate this immune response suppression. We show that the activation of both heterogeneous and cloned Ts cells is antigen-specific and MHC-restricted under our experimental conditions. After appropriate activation, the effector function of both cloned Lyt-1+,2-Ts cells and heterogeneous Lyt-1-,2+ Ts cells was also antigen-specific. In contrast, once activated, Ts cells suppressed the responses generated by cloned Th cells and hapten-primed B cells in an MHC-unrestricted fashion. We also showed, however, that a population of unprimed Lyt-1+,2-T cells was able to significantly alter the genetic restriction requirements for Ts cell function. The activity of this population was itself MHC-restricted, and was observed only when the unprimed Lyt-1+,2-T cells shared the MHC restriction specificity of the cloned Th cells functioning in a given response. When these requirements were satisfied, Lyt-1+,2- T cells significantly modified the suppression mediated by both heterogeneous and cloned Ts cells, resulting in suppression that was then MHC restricted in its effector function as well as in its activation requirements. Thus, our findings suggest that the observed MHC restriction in Ts function is the result of a complex interaction involving Ts cells, Th cells, and an additional population of MHC-restricted Lyt-1+,2- T cells. This newly characterized activity of Lyt-1+,2- T cells functionally resembles that of an MHC-restricted contrasuppressor population that selectively blocks a pathway of MHC-unrestricted Ts activity, while leaving intact susceptibility to MHC-restricted Ts effects.

scholarly journals Hyaluronate-CD44 Interactions Can Induce Murine B-Cell Activation

Blood ◽  
1997 ◽  
Vol 89 (8) ◽  
pp. 2901-2908 ◽  
Author(s):  
Asimah Rafi ◽  
Mitzi Nagarkatti ◽  
Prakash S. Nagarkatti
Keyword(s):  
T Cells ◽  
B Cells ◽  
B Cell ◽  
Cell Activation ◽  
Critical Role ◽  
Surface Glycoprotein ◽  
B Cell Differentiation ◽  
B Cell Activation ◽  
Cell Surface Glycoprotein ◽  
Immunodeficient Mice

Abstract CD44 is a widely distributed cell surface glycoprotein whose principal ligand has been identified as hyaluronic acid (HA), a major component of the extracellular matrix (ECM). Recent studies have demonstrated that activation through CD44 leads to induction of effector function in T cells and macrophages. In the current study, we investigated whether HA or monoclonal antibodies (MoAbs) against CD44 would induce a proliferative response in mouse lymphocytes. Spleen cells from normal and nude, but not severe combined immunodeficient mice, exhibited strong proliferative responsiveness to stimulation with soluble HA or anti-CD44 MoAbs. Furthermore, purified B cells, but not T cells, were found to respond to HA. HA was unable to stimulate T cells even in the presence of antigen presenting cells (APC) and was unable to act as a costimulus in the presence of mitogenic or submitogenic concentrations of anti-CD3 MoAbs. In contrast, stimulation of B cells with HA in vitro, led to B-cell differentiation as measured by production of IgM antibodies in addition to increased expression of CD44 and decreased levels of CD45R. The fact that the B cells were responding directly to HA through its binding to CD44 and not to any contaminants or endotoxins was demonstrated by the fact that F(ab)2 fragments of anti-CD44 MoAbs or soluble CD44 fusion proteins could significantly inhibit the HA-induced proliferation of B cells. Also, HA-induced proliferation of B cells was not affected by the addition of polymixin B, and B cells from lipopolysaccharide (LPS)-unresponsive C3H/HeJ strain responded strongly to stimulation with HA. Furthermore, HA, but not chondroitin-sulfate, another major component of the ECM, induced B-cell activation. It was also noted that injection of HA intraperitoneally, triggered splenic B cell proliferation in vivo. Together, the current study demonstrates that interaction between HA and CD44 can regulate murine B-cell effector functions and that such interactions may play a critical role during normal or autoimmune responsiveness of B cells.

scholarly journals T cell regulation of b cell activation. Cloned Lyt-1+2-T suppressor cells inhibit the major histocompatibility complex-restricted interaction of T helper cells with B cells and/or accessory cells.

1983 ◽  
Vol 158 (4) ◽  
pp. 1178-1190 ◽  
Author(s):  
Y Asano ◽  
R J Hodes
Keyword(s):  
Major Histocompatibility Complex ◽  
B Cells ◽  
Cell Activation ◽  
Suppressor Cells ◽  
Major Histocompatibility ◽  
T Helper ◽  
Th Cells ◽  
Effector Cells ◽  
Histocompatibility Complex ◽  
Accessory Cells

The present studies have identified cloned Lyt-1+2- T suppressor (Ts) cells that are both antigen specific and major histocompatibility complex (MHC) restricted in their activation requirements and that function to regulate the MHC-restricted activation of B cells by T helper (Th) cells. ParentA-restricted Ts clones suppressed, in antigen-specific fashion, the responses generated by (A X B)F1 Th cells cooperating with parentA (B plus accessory) cells, but did not suppress responses by the same (A X B)F1 Th cell population cooperating with parentB (B plus accessory) cells. Moreover, responses of (A X B)F1 leads to parentA Th cells and (A X B)F1 (B plus accessory) cells were suppressed by parentA-restricted Ts clones but not by parentB-restricted Ts clones. Thus, these findings suggest that the cloned Ts cells that have been characterized here function by specifically inhibiting the MHC-restricted interaction between Th cells and B and/or accessory cells. It was further demonstrated in experiments using cloned Th and Ts populations that these Lyt-1+2-Ts cells act not simply as inducers of suppressor but rather function in a restricted fashion as effector cells in the suppressor pathway.

scholarly journals Cytokine Overproduction, T-Cell Activation, and Defective T-Regulatory Functions Promote Nephritis in Systemic Lupus Erythematosus

2010 ◽  
Vol 2010 ◽  
pp. 1-6 ◽  
Author(s):  
Marco Tucci ◽  
Stefania Stucci ◽  
Sabino Strippoli ◽  
Francesco Silvestris
Keyword(s):  
Systemic Lupus Erythematosus ◽  
T Cells ◽  
B Cells ◽  
T Cell Activation ◽  
Lupus Erythematosus ◽  
Cell Activation ◽  
Cell Function ◽  
Inflammatory Cells ◽  
Systemic Lupus ◽  
Regulatory Functions

Lupus nephritis (LN) occurs in more than one-third of patients with systemic lupus erythematosus. Its pathogenesis is mostly attributable to the glomerular deposition of immune complexes and overproduction of T helper- (Th-) 1 cytokines. In this context, the high glomerular expression of IL-12 and IL-18 exerts a major pathogenetic role. These cytokines are locally produced by both macrophages and dendritic cells (DCs) which attract other inflammatory cells leading to maintenance of the kidney inflammation. However, other populations including T-cells and B-cells are integral for the development and worsening of renal damage. T-cells include many pathogenetic subsets, and the activation of Th-17 in keeping with defective T-regulatory (Treg) cell function regards as further event contributing to the glomerular damage. These populations also activate B-cells to produce nephritogenic auto-antibodies. Thus, LN includes a complex pathogenetic mechanism that involves different players and the evaluation of their activity may provide an effective tool for monitoring the onset of the disease.

scholarly journals T Cell Accumulation in B Cell Follicles Is Regulated by Dendritic Cells and Is Independent of B Cell Activation

2003 ◽  
Vol 197 (2) ◽  
pp. 195-206 ◽  
Author(s):  
Simon Fillatreau ◽  
David Gray
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
T Cell ◽  
B Cells ◽  
B Cell ◽  
Cell Activation ◽  
B Cell Activation ◽  
Cell Accumulation ◽  
Antigen Presenting ◽  
Deficient Mice

We investigated the mechanism of CD4 T cell accumulation in B cell follicles after immunization. Follicular T cell numbers were correlated with the number of B cells, indicating B cell control of the niche that T cells occupy. Despite this, we found no role for B cells in the follicular migration of T cells. Instead, T cells are induced to migrate into B cell follicles entirely as a result of interaction with dendritic cells (DCs). Migration relies on CD40-dependent maturation of DCs, as it did not occur in CD40-deficient mice but was reconstituted with CD40+ DCs. Restoration was not achieved by the activation of DCs with bacterial activators (e.g., lipopolysaccharide, CpG), but was by the injection of OX40L–huIgG1 fusion protein. Crucially, the up-regulation of OX40L (on antigen-presenting cells) and CXCR-5 (on T cells) are CD40-dependent events and we show that T cells do not migrate to follicles in immunized OX40-deficient mice.

scholarly journals Interaction of B cells with activated T cells reduces the threshold for CD40-mediated B cell activation

1999 ◽  
Vol 11 (1) ◽  
pp. 71-79 ◽  
Author(s):  
Gerry G. B. Klaus ◽  
Mary Holman ◽  
Caroline Johnson-Léger ◽  
Jillian R. Christenson ◽  
Marilyn R. Kehry
Keyword(s):  
T Cells ◽  
B Cells ◽  
B Cell ◽  
Cell Activation ◽  
B Cell Activation ◽  
Activated T Cells

Critical Role for CD81 in B Cell Activation.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1342-1342
Author(s):  
Mrinmoy Sanyal ◽  
Rosemary Fernandez ◽  
Shoshana Levy
Keyword(s):  
B Cells ◽  
B Cell ◽  
Cell Activation ◽  
Cell Function ◽  
Calcium Influx ◽  
Critical Role ◽  
B Cell Lymphoma ◽  
Free Calcium ◽  
B Cell Activation ◽  
Deficient Mice

Abstract CD81 is a component of the CD19/CD21 signaling complex in B cells. CD81 was originally discovered as target of an anti-proliferative antibody in a human B cell lymphoma. However, the exact role of CD81 in B cell function is not known. Here we studied B cells from CD81 knockout mice. We demonstrate that upon BCR induction these B cells flux higher intracellular free calcium ion; increase the phosphorylation of BCR-related proximal and distal substrates and increase their proliferation. Similarly, polyclonal activation of CD81-deficient B cells with LPS induced increased proliferation and antibody secretion. Consistent with these intrinsic B cell capabilities, CD81-deficient mice mounted significantly higher immune response upon antigenic stimulation. In addition, bone marrow perisinusoidal B cells (IgM+IgD+) capable of mounting T-independent immune responses against blood-borne pathogens were over represented in CD81-deficient mice. These cells also displayed increased calcium influx kinetics as splenic B cells and produced higher amounts of antibody after polyclonal stimulation. Taken together, these results suggest that CD81 is involved in suppressing B cell activation.

scholarly journals Antigen presentation by resting B cells. Radiosensitivity of the antigen-presentation function and two distinct pathways of T cell activation.

1984 ◽  
Vol 159 (3) ◽  
pp. 881-905 ◽  
Author(s):  
J D Ashwell ◽  
A L DeFranco ◽  
W E Paul ◽  
R H Schwartz
Keyword(s):  
Cell Proliferation ◽  
T Cells ◽  
T Cell ◽  
B Cells ◽  
B Cell ◽  
Antigen Presentation ◽  
Cell Activation ◽  
T Cell Proliferation ◽  
B Cell Activation ◽  
Antigen Presenting

In this report we have examined the ability of small resting B cells to act as antigen-presenting cells (APC) to antigen-specific MHC-restricted T cells as assessed by either T cell proliferation or T cell-dependent B cell stimulation. We found that 10 of 14 in vitro antigen-specific MHC-restricted T cell clones and lines and three of four T cell hybridomas could be induced to either proliferate or secrete IL-2 in the presence of lightly irradiated (1,000 rads) purified B cells and the appropriate foreign antigen. All T cell lines and hybridomas were stimulated to proliferate or make IL-2 by macrophage- and dendritic cell-enriched populations and all T cells tested except one hybridoma caused B cell activation when stimulated with B cells as APC. Furthermore, lightly irradiated, highly purified syngeneic B cells were as potent a source of APC for inducing B cell activation as were low density dendritic and macrophage-enriched cells. Lymph node T cells freshly taken from antigen-primed animals were also found to proliferate when cultured with purified B cells and the appropriate antigen. Thus, small resting B cells can function as APC to a variety of T cells. This APC function was easily measured when the cells were irradiated with 1,000 rads, but was greatly diminished or absent when they were irradiated with 3,300 rads. Thus, the failure of some other laboratories to observe this phenomenon may be the result of the relative radiosensitivity of the antigen-presenting function of the B cells. In addition, this radiosensitivity allowed us to easily distinguish B cell antigen presentation from presentation by the dendritic cell and macrophage, as the latter was resistant to 3,300 rads. Finally, one T cell clone that failed to proliferate when B cells were used as APC was able to recruit allogeneic B cells to proliferate in the presence of syngeneic B cells and the appropriate antigen. This result suggests that there are at least two distinct pathways of activation in T cells, one that leads to T cell proliferation and one that leads to the secretion of B cell recruitment factor(s).

scholarly journals Acute Csk inhibition hinders B cell activation by constraining the PI3 kinase pathway

2021 ◽  
Vol 118 (43) ◽  
pp. e2108957118
Author(s):  
Wen Lu ◽  
Katarzyna M. Skrzypczynska ◽  
Arthur Weiss
Keyword(s):  
T Cells ◽  
B Cells ◽  
B Cell ◽  
Cell Activation ◽  
Antigen Receptor ◽  
Negative Regulator ◽  
B Cell Activation ◽  
Cell Antigen Receptor ◽  
Cell Antigen ◽  
Bcr Signaling

T cell antigen receptor (TCR) and B cell antigen receptor (BCR) signaling are initiated and tightly regulated by Src-family kinases (SFKs). SFKs positively regulate TCR signaling in naïve T cells but have both positive and negative regulatory roles in BCR signaling in naïve B cells. The proper regulation of their activities depends on the opposing actions of receptor tyrosine phosphatases CD45 and CD148 and the cytoplasmic tyrosine kinase C-terminal Src kinase Csk. Csk is a major negative regulator of SFKs. Using a PP1-analog-sensitive Csk (CskAS) system, we have previously shown that inhibition of CskAS increases SFK activity, leading to augmentation of responses to weak TCR stimuli in T cells. However, the effects of Csk inhibition in B cells were not known. In this study, we surprisingly found that inhibition of CskAS led to marked inhibition of BCR-stimulated cytoplasmic free calcium increase and Erk activation despite increased SFK activation in B cells, contrasting the effects observed in T cells. Further investigation revealed that acute CskAS inhibition suppressed BCR-mediated phosphatidylinositol 3,4,5-trisphosphate (PIP3) production in B cells. Restoring PIP3 levels in B cells by CD19 cross-linking or SHIP1 deficiency eliminated the negative regulatory effect of CskAS inhibition. This reveals the critical role of Csk in maintaining an appropriate level of SFK activity and regulating PIP3 amounts as a means of compensating for SFK fluctuations to prevent inappropriate B cell activation. This regulatory mechanism controlling PIP3 amounts may also contribute to B cell anergy and self-tolerance.

scholarly journals Distinct functional phenotypes of cloned Ia-restricted helper T cells.

1985 ◽  
Vol 162 (1) ◽  
pp. 188-201 ◽  
Author(s):  
J Kim ◽  
A Woods ◽  
E Becker-Dunn ◽  
K Bottomly
Keyword(s):  
T Cells ◽  
B Cells ◽  
B Cell ◽  
Cell Activation ◽  
B Cell Activation ◽  
Functional Types ◽  
Precursor B Cells ◽  
Type 3

Analysis of activation of phosphorylcholine (PC)-specific B cells by a large number of different cloned, self Ia-specific helper T cell (Th) clones has permitted the classification of such T cells into four distinct functional types. Types 1 and 2 induce B cells to secrete anti-PC antibody in an antigen-specific, Ia-restricted fashion. Type 3 cells induce antigen-specific, Ia-restricted B cell proliferation, but do not lead to specific antibody formation, and have been shown previously to have suppressor functions. Type 4 cells are autoreactive, and induce antigen-independent B cell activation and antibody secretion. The distinction between type 1 and type 2 Th clones was analyzed in detail. In bulk cultures, type 1 cloned lines generate an idiotypically heterogeneous anti-PC antibody response, whereas type 2 cloned lines induce a larger response that is dominated by the T15 idiotype. In limiting-dilution analyses, type 2 cells induce fourfold more T15+, PC-specific precursor B cells than do type 1 cells, and in addition, induce larger burst sizes for T15+, PC-specific B cells. Type 4 clones can also be subdivided into cells that are type 1-like, and cells that are type 2-like. These differences in functional phenotype are seen over a broad range of antigen and cell doses. Detailed analysis of the behavior of these distinct functional types of Th should allow a better understanding of the functional properties of mixed populations of antigen-primed, Ia-restricted Th cells.

CD154 Blockade Prevents Allosensitization through Inhibiting Both T- and B-Cell Activation and Decreasing Expression of IFN-γ and IL-10 in T-Cells.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1346-1346
Author(s):  
Hong Xu ◽  
Jun Yan ◽  
Yiming Huang ◽  
Paula M. Chilton ◽  
Michael K. Tanner ◽  
...  
Keyword(s):  
T Cells ◽  
B Cells ◽  
B Cell ◽  
Cell Activation ◽  
Skin Grafting ◽  
Cell Populations ◽  
B Cell Activation ◽  
T And B Cells ◽  
Time Points ◽  
Ifn Γ

Abstract Recipient sensitization to MHC antigens from transfusion therapy and prior graft rejection is among the most critical of problems in clinical transplantation. Sensitized patients reject vascularized organ or bone marrow transplants within minutes to hours as a result of preformed anti-donor Abs. Preventing allosensitization at the time recipients are exposed to donor alloantigens would be of obvious clinical benefit. B cell activation and the generation of memory B cells depends upon T cell responses via signaling from the co-stimulatory molecule CD154 (on activated T cells) to CD40 (on B cells). We have demonstrated in an allogeneic mouse model [BALB/c (H2Kd) to B6 (H2Kb)] that blockade of T and B cell interactions with anti-CD154 induces B cell tolerance, as defined by complete abrogation of the generation of donor-specific Ab after skin grafting. Furthermore, anti-CD154 treatment promotes successful subsequent bone marrow transplantation in these recipients, confirming that sensitization was prevented. In this study, we evaluated the effect of anti-CD154 mAb on T- and B-cell populations, activation state, and cytokine expression by T cells. B6 recipients were treated with anti-CD154 (day 0 and +3) or isotype hamster IgG control around the time receiving BALB/c skin grafts (day 0), and the number of T-cells (CD4+ and CD8+), total B-cells (CD19+), immature B-cells (CD19+CD24highCD23low), and follicular B-cells (CD19+CD24lowCD23high) in the spleen was enumerated by 4 color flow cytometry at day 7, 15 and 25 after skin grafting. No significant difference in absolute number of T- and B-cell subpopulations was seen between anti-CD154 and control IgG treated groups at the time points tested. By measuring the percentage CD71+ cells in the CD8+ or CD4+ gate or CD69+ in the CD19+ gate, activated T and B cell populations were evaluated. In vivo blockade of CD154 resulted in a significantly reduced activation of alloreactive T- and B-cells: the percentage of CD8+/CD71+ T cells was significantly lower at day 7 and the percentage of CD4+/CD71+ T cells was significantly lower at all time points compared with control mice (P < 0.05). The percentage of CD19+/CD69+ B cells at day 7 and 25 was significantly lower compared with control IgG treated mice (P < 0.05). To determine the effect of anti-CD154 treatment on Th1 and Th2 cytokine production, intracellular IFN-γ and IL-10 expression was analyzed. The IFN-γ expression in both CD8 and CD4 T-cells was inhibited at day 7 and reached significance (P < 0.01) by day 15 compared with control IgG treated group. IL-10, a cytokine which promotes B-cell activation and differentiation expression, was similar at day 7 between the two groups, but significantly decreased in both CD8 and CD4 T-cells at day 15 in mice treated with anti-CD154. Therefore, these data suggest that blockade of CD154 during initial antigen exposure mechanistically interferes with activation of both allo antigen-specific T and B-cells and inhibits the generation of allogeneic Ab (allosensitization). These effects are associated with suppression of IFN-γ and IL-10 cytokine secretion. Figure Figure

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