scholarly journals Rational design of new CpG oligonucleotides that combine B cell activation with high IFN-α induction in plasmacytoid dendritic cells

2003 ◽  
Vol 33 (6) ◽  
pp. 1633-1641 ◽  
Author(s):  
Gunther Hartmann ◽  
Julia Battiany ◽  
Hendrik Poeck ◽  
Moritz Wagner ◽  
Miren Kerkmann ◽  
...  
2017 ◽  
Vol 114 (8) ◽  
pp. 1988-1993 ◽  
Author(s):  
Hong Zhang ◽  
Josh D. Gregorio ◽  
Toru Iwahori ◽  
Xiangyue Zhang ◽  
Okmi Choi ◽  
...  

Plasmacytoid dendritic cells (pDCs) are known mainly for their secretion of type I IFN upon viral encounter. We describe a CD2hiCD5+CD81+pDC subset, distinguished by prominent dendrites and a mature phenotype, in human blood, bone marrow, and tonsil, which can be generated from CD34+progenitors. These CD2hiCD5+CD81+cells express classical pDC markers, as well as the toll-like receptors that enable conventional pDCs to respond to viral infection. However, their gene expression profile is distinct, and they produce little or no type I IFN upon stimulation with CpG oligonucleotides, likely due to their diminished expression of IFN regulatory factor 7. A similar population of CD5+CD81+pDCs is present in mice and also does not produce type I IFN after CpG stimulation. In contrast to conventional CD5−CD81−pDCs, human CD5+CD81+pDCs are potent stimulators of B-cell activation and antibody production and strong inducers of T-cell proliferation and Treg formation. These findings reveal the presence of a discrete pDC population that does not produce type I IFN and yet mediates important immune functions previously attributed to all pDCs.


2009 ◽  
Vol 183 (11) ◽  
pp. 7140-7149 ◽  
Author(s):  
Chuanlin Ding ◽  
Yihua Cai ◽  
Jose Marroquin ◽  
Suzanne T. Ildstad ◽  
Jun Yan

2014 ◽  
Vol 4 (12) ◽  
pp. 1448-1465 ◽  
Author(s):  
Kristina Heinig ◽  
Marcel Gätjen ◽  
Michael Grau ◽  
Vanessa Stache ◽  
Ioannis Anagnostopoulos ◽  
...  

2019 ◽  
Vol 58 ◽  
pp. 44-52 ◽  
Author(s):  
William R Heath ◽  
Yu Kato ◽  
Thiago M Steiner ◽  
Irina Caminschi

2003 ◽  
Vol 197 (2) ◽  
pp. 195-206 ◽  
Author(s):  
Simon Fillatreau ◽  
David Gray

We investigated the mechanism of CD4 T cell accumulation in B cell follicles after immunization. Follicular T cell numbers were correlated with the number of B cells, indicating B cell control of the niche that T cells occupy. Despite this, we found no role for B cells in the follicular migration of T cells. Instead, T cells are induced to migrate into B cell follicles entirely as a result of interaction with dendritic cells (DCs). Migration relies on CD40-dependent maturation of DCs, as it did not occur in CD40-deficient mice but was reconstituted with CD40+ DCs. Restoration was not achieved by the activation of DCs with bacterial activators (e.g., lipopolysaccharide, CpG), but was by the injection of OX40L–huIgG1 fusion protein. Crucially, the up-regulation of OX40L (on antigen-presenting cells) and CXCR-5 (on T cells) are CD40-dependent events and we show that T cells do not migrate to follicles in immunized OX40-deficient mice.


2012 ◽  
Vol 209 (10) ◽  
pp. 1825-1840 ◽  
Author(s):  
Craig P. Chappell ◽  
Kevin E. Draves ◽  
Natalia V. Giltiay ◽  
Edward A. Clark

Dendritic cells (DCs) are best known for their ability to activate naive T cells, and emerging evidence suggests that distinct DC subsets induce specialized T cell responses. However, little is known concerning the role of DC subsets in the initiation of B cell responses. We report that antigen (Ag) delivery to DC-inhibitory receptor 2 (DCIR2) found on marginal zone (MZ)–associated CD8α− DCs in mice leads to robust class-switched antibody (Ab) responses to a T cell–dependent (TD) Ag. DCIR2+ DCs induced rapid up-regulation of multiple B cell activation markers and changes in chemokine receptor expression, resulting in accumulation of Ag-specific B cells within extrafollicular splenic bridging channels as early as 24 h after immunization. Ag-specific B cells primed by DCIR2+ DCs were remarkably efficient at driving naive CD4 T cell proliferation, yet DCIR2-induced responses failed to form germinal centers or undergo affinity maturation of serum Ab unless toll-like receptor (TLR) 7 or TLR9 agonists were included at the time of immunization. These results demonstrate DCIR2+ DCs have a unique capacity to initiate extrafollicular B cell responses to TD Ag, and thus define a novel division of labor among splenic DC subsets for B cell activation during humoral immune responses.


2000 ◽  
Vol 191 (2) ◽  
pp. 381-386 ◽  
Author(s):  
Norman Garceau ◽  
Yoko Kosaka ◽  
Sally Masters ◽  
John Hambor ◽  
Reiko Shinkura ◽  
...  

CD40 signaling in B cells and dendritic cells (DCs) is critical for the development of humoral and cell-mediated immunity, respectively. Nuclear factor κB (NF-κB)–inducing kinase (NIK) has been implicated as a central transducing kinase in CD40-dependent activation. Here, we show that although NIK is essential for B cell activation, it is dispensable for activation of DCs. Such data provide compelling evidence that different intermediary kinases are used by different cellular lineages to trigger NF-κB activation via CD40.


Blood ◽  
2013 ◽  
Vol 121 (1) ◽  
pp. 11-19 ◽  
Author(s):  
Priyanka Sathe ◽  
David Vremec ◽  
Li Wu ◽  
Lynn Corcoran ◽  
Ken Shortman

Abstract The developmental origin of IFN-producing plasmacytoid dendritic cells (pDCs) has been uncertain. In the present study, we tracked the development of pDCs in cultures of BM precursors stimulated with Flt3 ligand. Common myeloid precursors (CMPs) produced both conventional DCs (cDCs) and pDCs via the DC-restricted common DC precursor. Common lymphoid precursors (CLPs) produced only a few cDCs with variable efficiency, but produced pDCs via a transient intermediate precursor with B-cell potential. The pDCs of both origins produced IFN-α when stimulated with CpG oligonucleotides. The pDCs of CLP origin showed evidence of past RAG1 expression and had D-J rearrangements in IgH genes. Most pDCs and all cDCs of CMP origin lacked these signs of a lymphoid past. However, in these cultures, some pDCs of CMP origin showed evidence of past RAG1 expression and had D-J IgH gene rearrangements; most of these derived from a subset of CMPs already expressing RAG1.


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