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Human B cell respon...
Human B cell responses to TLR ligands are differentially modulated by myeloid and plasmacytoid dendritic cells
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- Douagi, I (författare)
- Karolinska Institutet
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Gujer, C (författare)
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- Sundling, C (författare)
- Karolinska Institutet
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Adams, WC (författare)
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Smed-Sorensen, A (författare)
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Seder, RA (författare)
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- Hedestam, GBK (författare)
- Karolinska Institutet
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- Lore, K (författare)
- Karolinska Institutet
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(creator_code:org_t)
- The American Association of Immunologists, 2009
- 2009
- Engelska.
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Ingår i: Journal of immunology (Baltimore, Md. : 1950). - : The American Association of Immunologists. - 1550-6606 .- 0022-1767. ; 182:4, s. 1991-2001
- Relaterad länk:
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http://www.jimmunol....
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http://kipublication...
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https://doi.org/10.4...
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Abstract
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- Selected TLR ligands are under evaluation as vaccine adjuvants and are known to activate dendritic cells (DCs) and B cells to affect vaccine-induced Ab responses. However, the relative contribution of the two main human DC subsets, myeloid (MDCs) and plasmacytoid (PDCs), in supporting B cell responses to TLR ligands remains poorly understood. We found that PDCs but not MDCs markedly enhanced B cell proliferation in response to TLR7/8-L, an imidazoquinoline derivative, and to a lesser extent to TLR9 ligands (CpG ODN classes A, B, and C). PDCs strongly enhanced TLR7/8-L-induced proliferation of both memory and naive B cells but were only able to support memory cells to differentiate to CD27high plasmablasts. In response to TLR7/8 stimulation, PDCs mediated the up-regulation of transcription factors B lymphocyte-induced maturation protein 1 and X-box binding protein 1 and enhanced differentiation of B cells into IgM-, IgG-, and IgA-producing cells. Type I IFN produced to high levels by PDCs was the principal mediator of the effects on TLR7/8 stimulation. Although MDCs expressed higher levels of the known B cell growth factors IL-6, IL-10, and B cell-activating factor in response to TLR7/8 stimulation, they were unable to enhance B cell responses in this system. These data help decipher the different roles of PDCs and MDCs for modulating human B cell responses and can contribute to selection of specific TLR ligands as vaccine adjuvants.
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