CD40-stimulated B Lymphocytes Pulsed with Tumor Antigens Are Effective Antigen-presenting Cells That Can Generate Specific T Cells
dc.contributor.author | Lapointe, Réjean | |
dc.contributor.author | Bellemare-Pelletier, Angélique | |
dc.contributor.author | Housseau, Frank | |
dc.contributor.author | Thibodeau, Jacques | |
dc.contributor.author | Hwu, Patrick | |
dc.date.accessioned | 2006-08-14T20:16:52Z | |
dc.date.available | 2006-08-14T20:16:52Z | |
dc.date.issued | 2003-06-01 | |
dc.identifier.uri | http://hdl.handle.net/1866/160 | |
dc.description.sponsorship | Intramural National Institutes of Health (NIH) program | en |
dc.format.extent | 280924 bytes | |
dc.format.mimetype | application/pdf | |
dc.publisher | HighWire Press (American Association for Cancer Research) | en |
dc.subject | Tumor antigen presentation; CD40-activated B lymphocytes | en |
dc.subject | CD4+ T lymphocytes; MHC class II; HLA-DO | en |
dc.title | CD40-stimulated B Lymphocytes Pulsed with Tumor Antigens Are Effective Antigen-presenting Cells That Can Generate Specific T Cells | en |
dc.type | Article | en |
dc.contributor.affiliation | Université de Montréal. Faculté de médecine. Département de médecine | fr |
dcterms.abstract | Although they are considered as antigen presenting cells (APC), the role of antigen-unspecific B-lymphocytes in antigen presentation and T lymphocyte stimulation remains controversial. In this paper, we tested the capacity of normal human peripheral activated B cells to stimulate T cells using melanoma antigens or melanoma cell lysates. B lymphocytes activated through CD40 ligation and then pulsed with tumor antigens efficiently processed and presented MHC class II restricted peptides to specific CD4+ T cell clones. This suggests that CD40-activated B cells have the functional and molecular competence to present MHC class II epitopes when pulsed with exogenous antigens, thereby making them a relevant source of APC to generate T cells. To test this hypothesis, CD40-activated B cells were pulsed with a lysate prepared from melanoma cells and used to stimulate peripheral autologous T cells. Interestingly, T cells specific to melanoma antigens were generated. Further analysis of these T cell clones revealed that they recognized MHC class II restricted epitopes from tyrosinase, a known melanoma tumor antigen. The efficient antigen presentation by antigen-unspecific activated B cells was correlated with a down-regulation in the expression of HLA-DO, a B cell specific protein known to interfere with HLA-DM function. Because HLA-DM is important in MHC class II peptide loading, the observed decrease in HLA-DO may partially explain the enhanced antigen presentation following B-cell activation. Results globally suggest that when they are properly activated, antigen-unspecific B-lymphocytes can present exogenous antigens by MHC class II molecules and stimulate peripheral antigen-specific T cells. Antigen presentation by activated B cells could be exploited for immunotherapy by allowing the in vitro generation of T cells specific against antigens expressed by tumors or viruses. | en |
dcterms.language | eng | en |
UdeM.VersionRioxx | Version acceptée / Accepted Manuscript | |
oaire.citationTitle | Cancer research | |
oaire.citationVolume | 63 | |
oaire.citationStartPage | 2836 | |
oaire.citationEndPage | 2843 |
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