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Plos One : the Role of the E3 Ligase Cbl-b in Murine Dendritic Cells, Volume 8

By Platten, Michael

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Book Id: WPLBN0003968478
Format Type: PDF eBook :
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Reproduction Date: 2015

Title: Plos One : the Role of the E3 Ligase Cbl-b in Murine Dendritic Cells, Volume 8  
Author: Platten, Michael
Volume: Volume 8
Language: English
Subject: Journals, Science, Medical Science
Collections: Periodicals: Journal and Magazine Collection (Contemporary)
Publication Date:
Publisher: Plos


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Platten, M. (n.d.). Plos One : the Role of the E3 Ligase Cbl-b in Murine Dendritic Cells, Volume 8. Retrieved from

Description : Dendritic cells (DCs) are potent antigen-presenting cells with a promising potential in cancer immunotherapy. Cbl proteins are E3 ubiquitin ligases and have been implicated in regulating the functional activity of various immune cells. As an example, c-Cbl negatively affects DC activation. We here describe that another member of the Cbl-protein family (i.e. Cbl-b) is highly expressed in murine bone-marrow-derived DCs (BMDCs). Differentiation of cblb2/2 bone marrow mononuclear cells into classical BMDCs is unaltered, except enhanced induction of DEC-205 (CD205) expression. When tested in mixedlymphocyte reaction (MLR), cblb2/2 BMDCs exhibit increased allo-stimulatory capacity in vitro. BMDCs were next in vitro stimulated by various toll like receptor (TLR)-agonists (LPS, Poly(I:C), CpG) and exposed to FITC-labeled dextran. Upon TLRstimulation, cblb2/2 BMDCs produce higher levels of proinflammatory cytokines (IL-1a, IL-6 and TNF-a) and exhibit a slightly higher level of FITC-dextran uptake. To further characterize the functional significance of cblb2/2 BMDCs we tested them in antigen-specific T cell responses against ovalbumin (OVA) protein and peptides, activating either CD8+ OT-I or CD4+ OT-II transgenic T cells. However, cblb2/2 BMDCs are equally effective in inducing antigen-specific T cell responses when compared to wildtype BMDCs both in vitro and in vivo. The migratory capacity into lymph nodes during inflammation was similarly not affected by the absence of Cbl-b. In line with these observations, cblb2/2 peptide-pulsed BMDCs are equally effective vaccines against OVA-expressing B16 tumors in vivo when compared to wildtype BMDCs. We conclude that in contrast to c-Cbl, Cbl-b plays only a limited role in the induction of Ag-specific T cell responses by murine BMDCs in vitro and in vivo.


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