A multimerized form of recombinant human CD40 ligand supports long-term activation and proliferation of B cells

García-Márquez, María; Shimabukuro‐Vornhagen, Alexander; Theurich, Sebastian; Kochanek, Matthias; Weber, Tanja; Wennhold, Kerstin; Dauben, Alexandra; Dzionek, Andrzej; Reinhard, Claudia; Bergwelt‐Baildon, Michael von

doi:10.1016/j.jcyt.2014.05.011

Cited by 13 publications

(14 citation statements)

References 28 publications

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“…Several strategies have been investigated to exploit CD40-CD40L interaction for the generation of antigen-presenting B cells (summarized in Table 1 for human B cells ) [reviewed in 21]. These include the usage of recombinant soluble CD40L proteins [22-25], triggering CD40 with agonistic monoclonal CD40 antibodies [26, 27], and CD40L-expressing feeder cells [28-30]. A number of factors affect the extent of B-cell activation by CD40-mediated signals.…”

Section: Generation Of Antigen-presenting B Cellsmentioning

confidence: 99%

“…Typically, human peripheral blood mononuclear cells (PBMCs) or purified B cells are cultured for a period of at least 14 days in the presence of the soluble CD40L and IL-4 [22, 23], in which the addition of IL-4 is necessary for B-cell proliferation [34]. These culture conditions result in a profound polyclonal activation of B cells that leads to an approximately 20-fold expansion [15, 35, 36] and the acquisition of an antigen-presenting phenotype [15, 37, 38].…”

Section: Generation Of Antigen-presenting B Cellsmentioning

confidence: 99%

“…The ability of human CD40B cells to expand antigen-experienced CD4+ T cells, but also to prime naïve CD4+ T cells was demonstrated in several studies [15, 17, 22, 24, 26, 35, 37, 44, 45]. Lapointe et al [37] showed that when pulsed with tumor lysates, CD40B cells expanded and activated tumor antigen-specific memory CD4+ T cells from the blood of cancer patients.…”

Section: Generation Of Antigen-presenting B Cellsmentioning

confidence: 99%

“…The recent development of a GMP-grade CD40-activating reagent has been one of the important steps towards the clinical testing of a CD40B cell-based cancer vaccine [22]. This B cell-activating reagent has overcome some of the problems described above with other activating reagents, i.e., xenogeneic components or poor proliferation.…”

Section: Clinical Application Of B Cell-based Cancer Vaccinesmentioning

confidence: 99%

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B Cell-Based Cancer Immunotherapy

Wennhold

Shimabukuro‐Vornhagen

Bergwelt‐Baildon

2019

Transfus Med Hemother

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B cells are not only producers of antibodies, but also contribute to immune regulation or act as potent antigen-presenting cells. The potential of B cells for cellular therapy is still largely underestimated, despite their multiple diverse effector functions. The CD40L/CD40 signaling pathway is the most potent activator of antigen presentation capacity in B lymphocytes. CD40-activated B cells are potent antigen-presenting cells that induce specific T-cell responses in vitro and in vivo. In preclinical cancer models in mice and dogs, CD40-activated B cell-based cancer immunotherapy was able to induce effective antitumor immunity. So far, there have been only few early-stage clinical studies involving B cell-based cancer vaccines. These trials indicate that B cell-based immunotherapy is generally safe and associated with little toxicity. Furthermore, these studies suggest that B-cell immunotherapy can elicit antitumor T-cell responses. Alongside the recent advances in cellular therapies in general, major obstacles for generation of good manufacturing practice-manufactured B-cell immunotherapies have been overcome. Thus, a first clinical trial involving CD40-activated B cells might be in reach.

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Section: Generation Of Antigen-presenting B Cellsmentioning

confidence: 99%

Section: Generation Of Antigen-presenting B Cellsmentioning

confidence: 99%

Section: Generation Of Antigen-presenting B Cellsmentioning

confidence: 99%

Section: Clinical Application Of B Cell-based Cancer Vaccinesmentioning

confidence: 99%

See 2 more Smart Citations

B Cell-Based Cancer Immunotherapy

Wennhold

Shimabukuro‐Vornhagen

Bergwelt‐Baildon

2019

Transfus Med Hemother

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“…The low numbers of circulating dendritic cells (DC) and macrophages in blood and their limited capacity for proliferation in vitro limit their applications (32–34). In contrast, B cells are more abundant in circulating blood and easier to expand in vitro compared to DC and macrophages (35–37). To that end, B cells offer a useful and, potentially, a more convenient source of APC.…”

Section: Introductionmentioning

confidence: 99%

Efficient Culture of Human Naive and Memory B Cells for Use as APCs

Watanabe

Yeh

et al. 2016

The Journal of Immunology

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The ability to culture and expand B cells in vitro has become a useful tool for studying human immunity. A limitation of current methods for human B-cell culture is the capacity to support mature B-cell proliferation. We have developed a culture method to support the efficient activation and proliferation of both naïve and memory human B cells. This culture supports extensive B-cell proliferation, with approximately 103-fold increases following 8 days in culture, and 106-fold increases when cultures are split and cultured for 8 more days. In culture, a significant fraction of naïve B cells undergo isotype switching and differentiate into plasmacytes. Culture-derived (CD) B cells are readily cryopreserved, and when recovered, retain their ability to proliferate and differentiate. Significantly, proliferating CD B cells express high levels of MHCII, CD80, and CD86. CD B cells act as APCs and present both alloantigens and microbial antigens to T cells. We are able to activate and expand antigen-specific memory B cells; these cultured cells are highly effective in presenting antigen to T cells. We have characterized the TCR repertoire of rare antigen-specific CD4+ T cells that proliferated in response to tetanus toxoid (TT) presented by autologous CD B cells. TCR Vβ usage by TT-activated CD4+ T cells differs from both resting and unspecifically activated CD4+ T cells. Moreover, we found that TT-specific TCR Vβ usage by CD4+ T cells was substantially different between donors. This culture method provides a platform for studying the BCR and TCR repertoires within a single individual.

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A tetrameric form of CD40 ligand with potent biological activities in both mouse and human primary B cells

Lai

Xiong

et al. 2019

Molecular Immunology

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A multimerized form of recombinant human CD40 ligand supports long-term activation and proliferation of B cells

Cited by 13 publications

References 28 publications

B Cell-Based Cancer Immunotherapy

B Cell-Based Cancer Immunotherapy

Efficient Culture of Human Naive and Memory B Cells for Use as APCs

A tetrameric form of CD40 ligand with potent biological activities in both mouse and human primary B cells

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