scholarly journals MHC Disparate Resting B Cells Are Tolerogenic in the Absence of Alloantigen-Expressing Dendritic Cells

2013 ◽  
Vol 2013 ◽  
pp. 1-8
Author(s):  
Hugh I. McFarland ◽  
Kazuhide Tsuji ◽  
Karen P. Mason ◽  
Amy S. Rosenberg
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
B Cells ◽  
Transgenic Mice ◽  
Mhc Class I ◽  
Graft Rejection ◽  
Parental Strain ◽  
Soluble Proteins ◽  
Cell Populations ◽  
T And B Cells

Resting B cell (rB) populations have been shown to tolerize to soluble proteins and to minor-H but not to MHC alloantigens. We speculated that the reason for failing to tolerize to MHC alloantigen is that the few remaining dendritic cells (DCs) contaminating purified rB cell populations efficiently activate MHC allospecific T cells which are present at a higher frequency than T cells specific for minor-H alloantigen and soluble proteins. We established that MHC disparate rB cells are indeed tolerogenic when devoid of DC populations, as parental strain mice showed delayed skin graft rejection when infused with rB cells from mice in which MHC class I alloantigen was specifically targeted to T and B cells (CD2- transgenic mice). In contrast, treatment of parental strain mice with allogeneic rB cells purified from MHC- transgenic mice, in which is ubiquitously expressed, including DCs, induced accelerated graft rejection. We also showed that adding only 5,000 expressing DCs to CD2- rB cells abrogated the tolerogenic effect. Surprisingly, allogeneic rB cells prolonged graft survival in -primed mice. Thus, MHC disparate rB cells are tolerogenic and their failure to delay graft rejection can be explained by contaminating allogeneic DCs.

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

scholarly journals Collaboration of histoincompatible T and B lymphocytes using cells from tetraparental bone marrow chimeras.

1975 ◽  
Vol 142 (4) ◽  
pp. 989-997 ◽  
Author(s):  
H von Boehmer ◽  
L Hudson ◽  
J Sprent
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
B Cells ◽  
B Cell ◽  
B Lymphocytes ◽  
Parental Strain ◽  
Secondary Response ◽  
Cell Populations ◽  
Sheep Erythrocytes ◽  
Bone Marrow Chimeras

T-B collaboration has been studied in a secondary response to sheep erythrocytes using either syngeneic or allogeneic T- and B-cell combinations. T cells prepared from tetraparental bone marrow chimeras (TBMC), carrying H-2 determinants of one parental strain only, cooperated with syngeneic, as well as with allogeneic B cells carrying the alloantigens to which the T cells had been tolerized in the chimeric environment. When TBMC-derived cells of a single H-2 specificity were transferred with a mixture of TBMC-derived B cells of both H-2 types of the parental strains, no preference for syngeneic cooperation was found. The data therefore suggest that the presence of differing H-2-complex determinants on the allogeneic T- and B-cell populations of the two different strain combinations tested do not interfere with T-B collaboration when the cell populations studied are mutually tolerant.

scholarly journals B Cells and Dendritic Cells from Vκ8 Light Chain Transgenic Mice Activate MRL-lpr/gld CD4+ T Cells

2006 ◽  
Vol 177 (1) ◽  
pp. 45-52 ◽  
Author(s):  
Britte C. Beaudette-Zlatanova ◽  
Tina Ling ◽  
Mark J. Shlomchik ◽  
Ann Marshak-Rothstein ◽  
Ian R. Rifkin
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
B Cells ◽  
Transgenic Mice ◽  
Light Chain ◽  
Cd4 T Cells

scholarly journals Comparison of DNA repair and radiosensitivity of different blood cell populations

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Daniel Heylmann ◽  
Viviane Ponath ◽  
Thomas Kindler ◽  
Bernd Kaina
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cells ◽  
Blood Cell ◽  
Peripheral Blood ◽  
Cell Populations ◽  
T And B Cells ◽  
Myeloid Lineage ◽  
Γh2ax Foci

AbstractDespite the frequent use of ionising radiation (IR) in therapy and diagnostics and the unavoidable exposure to external radiation sources, our knowledge regarding the radiosensitivity of human blood cell populations is limited and published data, obtained under different experimental conditions, are heterogeneous. To compare the radiosensitivity of different hematopoietic cell populations, we set out to determine the responses of cells obtained from peripheral blood of healthy volunteers under identical conditions (resting, non-stimulated cells). First, we measured the radiation response of T cells (Treg, Th, CTL), B cells, NK cells, CD34+ progenitor cells and monocytes obtained from peripheral blood and monocyte-derived macrophages (Mph) and immature dendritic cells (iDC) ex vivo and show that T and B cells are highly sensitive, starting to undergo apoptosis following IR with a dose as low as 0.125 Gy. Importantly, there was no clear threshold dose and cell death/apoptosis increased up to a saturation level with a dose of 2 Gy. The sensitivity decreased in the order of T cells > NK and B cells > monocytes > macrophages and iDC. The data confirm a previous report that Mph and iDC are radiation-resistant compared to their progenitor monocytes. Although non-stimulated T and B cells were highly radiation-sensitive compared to monocytes and macrophages, they were competent in the repair of DNA double-strand breaks, as shown by a decline in γH2AX foci in the post-exposure period. CD34+ cells obtained from peripheral blood also showed γH2AX decline post-exposure, indicating they are repair competent. Granulocytes (CD15+) did not display any γH2AX staining following IR. Although peripheral blood lymphocytes, the main fraction are T cells, were significantly more radiation-sensitive than monocytes, they displayed the expression of the repair proteins XRCC1, ligase III and PARP-1, which were nearly non-expressed in monocytes. To assess whether monocytes are depleted in vivo following IR, we measured the amount of T cells and monocytes in cancer patients who received total-body radiation (TBR, 6 × 2 Gy). We observed that the number of T cells in the peripheral blood significantly declined already after the first day of TBR and remained at a low level, which was accompanied by an increase in the number of γH2AX foci in the surviving CD3+ T cell fraction. In contrast, the number of monocytes did not decline extensively, reflecting their radiation resistance compared to T cells. Monocytes also showed an accumulation of γH2AX foci in vivo, but the levels were significantly lower than in T cells. CD56+ NK cells displayed a response similar to T cells. The data support the notion that unstimulated T cell subfractions are nearly equally radiation sensitive. There are, however, remarkable differences in the radiation sensitivity between the lymphoid and the myeloid lineage, with lymphoid cells being significantly more sensitive than cells of the myeloid lineage. In the myeloid lineage, macrophages and iDCs were the most radio-resistant cell types.

Primary Antigen-Specific B Cells: A Novel Approach to Cellular-Based Immunotherapy.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3717-3717
Author(s):  
Tahamtan Ahmadi ◽  
Nathalie Weizmann ◽  
Yvonne A. Efebera ◽  
David H. Sherr
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
T Cell ◽  
B Cells ◽  
B Cell ◽  
Mhc Class I ◽  
Class I ◽  
Protein Antigens ◽  
Cognate Protein ◽  
Activated B Cells

Abstract Background: The potential for CD40 ligand (CD40L)-activated B cells to serve as antigen-presenting cells (APC) for cell-based immunotherapy has been suggested. Unlike dendritic cells (DC), CD40L-activated B cell populations are readily expandable in vitro. In addition, antigen-specific B cells may efficiently uptake, process, and present cognate protein antigens. Nevertheless, important questions regarding the relative efficacy of CD40L-activated B cells as cell-based vaccines remain. Here, we exploited the unique ability of B cells to uptake antigen through their B cell receptor (BCR) and the propensity for CD40L-activated B cells, including antigen-specific clones, to grow in culture and to process cognate protein antigens to determine if CD40L-activated B cells represent a suitable substitute for dendritic cells for cell-based immunotherapy. Methods: As a head to head comparison between CD40L-activated B cells and mature DC, CD40L-activated B cells and bone marrow-derived DC were pulsed with MHC II- or MHC I-restricted self protein-derived (MOG; MBP) peptides and tested for their ability to induce proliferation of CD4+ or CD8+ clones. To compare processing and presentation of foreign protein antigens, C57BL/6 mice were immunized with 200 mg NP-BSA or an equivalent volume of PBS emulsified in CFA, sacrificed 10 days later and splenocytes obtained to generate antigen-specific CD40L-activated B cells and T cells. Bone marrow cells from PBS/CFA immunized mice were used to generate DCs. CD40L-activated (antigen-specific) B cells and DC were pulsed with NP-BSA, NP-CGG, or BSA and assayed for their ability to induce proliferation of primary T cells. Results: B cell populations were readily expanded by culture on CD40L transfected L cells. CD40L stimulation significantly up-regulated MHC class I and II expression and induced expression of CD80 and CD86 to levels similar to those detected on mature DCs. CD40L-activated B cells were comparable to DCs when presenting MHC class I- or II-restricted self-peptides to T cell clones. When presenting cognate protein antigen (NP-BSA or BSA) to primary T cells, CD40L-activated B cells from NP-BSA immunized mice were as efficient as DC, both of which induced a 13–15 fold increase in T cell proliferation. To determine if the hapten moiety is sufficient to increase antigen up-take and presentation, DCs and CD40L-activated B cells from NP-BSA immunized mice were pulsed with NP-CGG and used as APC for T cells from NP-BSA immunized mice. DCs induced significant responses comparable to those seen with BSA and NP-BSA. Activated B cells from NP-BSA-immunized mice induced significantly higher responses to NP-CGG than activated B cells from control PBS/CFA “immunized” mice, although these responses were lower than those generated with dendritic cells. Conclusion:CD40L-activated B cells can be readily expanded in vitroand significantly up-regulate co-stimulatory molecules CD80 and CD86 to levels comparable to mature DCs,CD40L-activated B cells present MHC class I- and II-restricted self-peptides to T cell clones as efficiently as mature DCs,Antigen-primed B cells are as efficient at presenting cognate protein antigens as DCs, Immunization with a hapten-carrier is sufficient to induce hapten-specific B cells which, when activated with CD40L, effectively present unrelated neoantigens conjugated with the hapten. The data suggest that CD40L-activated B cells represent an important alternative APC for immunotherapy, particularly when previously educated to protein or haptenic determinants.

scholarly journals Interstitial mononuclear cell populations in renal graft rejection. Identification by monoclonal antibodies in tissue sections

1982 ◽  
Vol 155 (1) ◽  
pp. 17-30 ◽  
Author(s):  
JL Platt ◽  
TW LeBien ◽  
AF Michael
Keyword(s):  
T Cells ◽  
Monoclonal Antibodies ◽  
B Cells ◽  
Graft Rejection ◽  
Blood Cells ◽  
Mononuclear Cells ◽  
Interstitial Cells ◽  
Cell Populations ◽  
Renal Graft ◽  
Renal Graft Rejection

The interstitial mononuclear cell populations of 22 renal grafts with interstitial rejection (IR), 6 grafts with interstitial nephritis without rejection (IN), and 5 kidneys without infiltration (3 donor kidneys, 2 grafts) were identified and quantitated by monoclonal antibodies recognizing T cells (TA-1, OKT3), helper inducer cells (OKT4), cytotoxic/suppressor cells (OKT8), B cells (BA-1), and monocytes and null cells (OKM1). Double-layer fluorochrome enhancement using F(ab')(2) reagents and nuclear counter staining with ethidium bromide enabled quantitation of the number of positive mononuclear cells, interstitial cells, and total cells on each of 30-55 microscopic fields per tissue section. T cells were the most abundant infiltrating cell in tissues with IR (35 +/- 9.8 percent), significantly higher than that seen in IN (21 +/- 16 percent) or in kidneys without infiltration (5.0 +/- 3.9 percent). The percentage of T cells identified by TA-1 or OKT3 was approximately equivalent to the summation of OKT4 plus OKT8. Although no differences were observed in the percentage of OKT4 cells, the percentage of OKT8 was significantly higher in IR (26 +/- 7.7 percent, P {less than} 10(-4)) than in IN (9.3 +/- 6.2 percent) or in kidneys with normal interstitium (3.0 +/- 2.4 percent). The ratio of OKT8/OKT4-positive T cells in 22 graft tissues with IR (3.2 +/- 1.4) was greater (P {less than} 0.0007) than 6 graft tissues with IN without rejection (0.82 +/- 0.39) and the 5 kidney tissues without interstitial infiltration (0.75 +/- 0.25). There was no significant difference between the groups in the relatively low percentage of interstitial cells identified as B cells reacting with BA-1 or containing S(IgD,M). The percentage of interstitial cells recognized by OKM1 was similar in rejection and interstitial nephritis, with both being greater than controls (P {less than} 0.02). The relative numbers of blood mononuclear cells identified by the monoclonal antibodies was generally not predictive of the proportions present in kidney tissue, although OKT4-positive blood cells were less numerous and OKMI+ blood cells were more numerous than in controls (P {less than} 0.002). Quantitative analysis of identifiable interstitial cells in graft rejection reveals that most infiltrating cells are T cells, the greater proportion of which are recognized by OKT8. OKT8-positive cells may play an important role in mediating renal graft rejection.

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