A Renewable Source of Donor Cells for Repetitive Monitoring of T- and B-Cell Alloreactivity

Zand, Martin S.; Bose, Anirban; Vo, Thuong; Coppage, Myra; Pellegrin, Tina; Arend, Lois J.; Lee, F. Eun-Hyung; Bozorgzadeh, Adel; Leong, Nufatt

doi:10.1111/j.1600-6143.2003.00637.x

Cited by 37 publications

(34 citation statements)

References 48 publications

(46 reference statements)

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“…14 Human plasmablast expression of CD138 is modulated by the local bone marrow environment, including the presence of IL-6, [15][16][17][18] IL-21, 13,16,19 and interferon-␣. 16,17,20 Signaling via CD138 by insulin-like growth factor and human hepatocyte growth factor (hHGF) appears to rescue normal plasmablasts from apoptosis. 16,19,20 We were therefore interested in determining if a large percentage of activated B cells could be driven to express CD138 given the appropriate in vitro culture conditions.…”

Section: Introductionmentioning

confidence: 99%

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CpG DNA activation and plasma-cell differentiation of CD27− naive human B cells

Huggins¹,

Pellegrin²,

Felgar³

et al. 2006

Blood

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130

137

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Unmethylated CpG DNA activation of naive CD27 ؊ B cells has been reported to require B-cell-receptor (BCR) cross-linking. We describe a culture system using CpG DNA with sequential steps for T-cell-independent activation of naive CD19 ؉ CD27 ؊ human peripheral blood B cells that induces efficient CD138 ؉ plasma-cell differentiation. CD27 ؉ and CD27 ؊ B cells were cultured in a 3-step system: (1)

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Section: Introductionmentioning

confidence: 99%

“…16,17,20 Signaling via CD138 by insulin-like growth factor and human hepatocyte growth factor (hHGF) appears to rescue normal plasmablasts from apoptosis. 16,19,20 We were therefore interested in determining if a large percentage of activated B cells could be driven to express CD138 given the appropriate in vitro culture conditions.…”

Section: Introductionmentioning

confidence: 99%

CpG DNA activation and plasma-cell differentiation of CD27− naive human B cells

Huggins¹,

Pellegrin²,

Felgar³

et al. 2006

Blood

Self Cite

130

137

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“…Although donor specificity is a major strength of each assay described here, repetitive monitoring of antidonor responses using these assays requires that a significant number of donor cells be available over an extended period of time. A technique to generate and sustain donor cells for use in monitoring assays after transplantation was described recently (58). Purified …”

Section: Flow Cytometric Detection Of Intracellular Cytokinesmentioning

confidence: 99%

How Can We Measure Immunologic Tolerance in Humans?

Najafian

Albin²,

Newell³

2006

Journal of the American Society of Nephrology

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Prevention and treatment of allograft rejection in organ transplant recipients relies primarily on non-antigen-specific immunosuppression, with all its associated potential hazards and costs. Currently, the status of the recipient immune response is measured by monitoring pharmacologic drug levels and clinical/pathologic evaluation of graft function. Development of reliable assays that can measure accurately the status of the immune response not only would help clinicians customize the prescription of immunosuppressive drugs in individual patients but also may allow their complete withdrawal in some patients with immunologic tolerance. Furthermore, these assays would facilitate the safe evaluation of novel tolerogenic regimens. Achieving this goal has proved to be very difficult because it requires both a more in-depth understanding of complex mechanisms of tolerance and also identification of transplant patients with acquired tolerance to an allograft that can be studied. This review discusses the current understanding of tolerance mechanisms and outlines the unique and specific challenges in development of tolerance/monitoring assays in the field of transplantation. In addition, several of the most promising candidate assays are discussed in detail.

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“…CD138 ϩ cells were then incubated with anti-CD138 antibodies coupled with magnetic beads and positively selected on a magnetic affinity column (Miltenyi Biotech, Auburn, CA) as previously described. 17,23 The resulting cells were then washed twice in PBS and used for experiments. The percentage of myeloma infiltrate in the bone marrow was quantified by flow cytometric analysis of -and -light chain expression as previously described.…”

mentioning

confidence: 99%

“…CD40L-stimulated human B cells and CpG-generated human plasma cells were prepared and cultured as previously described. 17,22,23 Human bone marrow stromal cells were isolated from bone marrow aspirates of healthy volunteers and cultured as previously described. 24…”

mentioning

confidence: 99%

Apoptosis and complement-mediated lysis of myeloma cells by polyclonal rabbit antithymocyte globulin

Zand

Pellegrin

et al. 2006

Blood

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Current monoclonal antibody therapies for multiple myeloma have had limited success, perhaps due to narrow target specificity. We have previously described the ability of polyclonal rabbit antithymo-cyte globulin (rATG) to induce caspase-and cathepsin-mediated apoptosis in human B and plasma cells. We now extend this observation to myeloma cells. Complement independent cell death was measured after addition of rATG (1-1000 g/mL) to cultures of myeloma cell lines or primary CD138 isolates from patient bone marrow aspirates. rATG induced significant levels of apoptosis in my-eloma cells as assayed by caspase induction , annexin V binding, subdiploid DNA fragmentation, plasma-membrane per-meability, and loss of mitochondrial-membrane potential. Addition of complement greatly augmented myeloma-cell death. Binding of rATG to individual my-eloma cell-surface proteins, primarily CD38, CD52, CD126, and CD138, was demonstrated by competitive inhibition experiments with targeted monoclonal antibod-ies. Three pathways of cell death were identified involving caspase activation, cathepsin D, and the genistein sensitive tyrosine kinase pathway. F(ab) 2 fragments of rATG had reduced proapoptotic activity, which was restored by coincuba-tion with Fc fragments, and anti-CD32 or anti-CD64 antibodies. We conclude that rATG is an effective agent for in vitro induction of apoptosis in multiple myeloma, and that exploratory clinical trials may be warranted. (Blood. 2006;107:2895-2903)

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A Renewable Source of Donor Cells for Repetitive Monitoring of T- and B-Cell Alloreactivity

Cited by 37 publications

References 48 publications

CpG DNA activation and plasma-cell differentiation of CD27− naive human B cells

CpG DNA activation and plasma-cell differentiation of CD27− naive human B cells

How Can We Measure Immunologic Tolerance in Humans?

Apoptosis and complement-mediated lysis of myeloma cells by polyclonal rabbit antithymocyte globulin

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