The SWHEL System for High-Resolution Analysis of In Vivo Antigen-Specific T-Dependent B Cell Responses

2015 ◽  
pp. 103-123 ◽  
Author(s):  
R. Brink ◽  
D. Paus ◽  
K. Bourne ◽  
J. R. Hermes ◽  
S. Gardam ◽  
...  
Keyword(s):  
High Resolution ◽  
B Cell ◽  
Cell Responses ◽  
High Resolution Analysis ◽  
Resolution Analysis ◽  
B Cell Responses

Agonist for Toll-Like Receptor (TLR) 9 Amplifies as Well as Inhibits the Differentiation of FVIII-Specific Memory B Cells into Antibody-Producing Plasma Cells in Vitro and in Vivo.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3382-3382
Author(s):  
Peter Allacher ◽  
Christina Hausl ◽  
Aniko Ginta Pordes ◽  
Rafi Uddin Ahmad ◽  
Hartmut J Ehrlich ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Memory B Cells ◽  
Memory B Cell ◽  
Cpg Dna ◽  
Cell Responses ◽  
Specific Memory ◽  
B Cell Responses

Abstract Memory B cells are essential for maintaining long-term antibody responses. They can persist for years even in the absence of antigen and are rapidly re-stimulated to differentiate into antibody-producing plasma cells when they encounter their specific antigen. Previously we demonstrated that ligands for TLR 7 and 9 amplify the differentiation of FVIII-specific memory B cells into anti-FVIII antibody-producing plasma cells at low concentrations of FVIII and prevent the inhibition of memory-B-cell differentiation at high concentrations of FVIII. The modulation of FVIII-specific memory-B-cell responses by agonists for TLR is highly relevant for the design of new immunotherapeutic approaches in patients with FVIII inhibitors because TLR are activated by a range of different viral and bacterial components. Specifically, TLR 7 is triggered by single-stranded RNA derived from viruses and TLR 9 is triggered by bacterial DNA containing unmethylated CpG motifs. We further explored the modulation of FVIII-specific memory-B-cell responses by agonists for TLRs by studying a broad range of concentrations of CpG DNA, a ligand for TLR 9, both in vitro and in vivo using the murine E17 model of hemophilia A. We used CpG-DNA in concentrations ranging from 0.1 to 10,000 ng/ml to study the modulation of FVIII-specific memory-B-cell responses in vitro and verified the specificity of the effects observed by including a blocking agent for TLR 9 and GpC-DNA, a non-stimulating negative control for CpG DNA. Furthermore, we used doses of CpG DNA ranging from 10 to 50,000 ng per dose to study the modulation of FVIII-specific memory-B-cell responses in vivo. E17 hemophilic mice were treated with a single intravenous dose of 200 ng FVIII to stimulate the generation of FVIII-specific memory B cells and were subsequently treated with another dose of FVIII that was given together with CpG DNA. We analyzed titers of anti-FVIII antibodies in the circulation of these mice one week after the second dose of FVIII. Previously we had shown that a single dose of 200 ng FVIII, given intravenously to E17 hemophilic mice, stimulates the formation of FVIII-specific memory B cells but is not sufficient to induce anti-FVIII antibodies that would be detectable in the circulation. Our results demonstrate a biphasic effect of CpG DNA on the re-stimulation of FVIII-specific memory B cells and their differentiation into antibody-producing plasma cells. Both in vitro and in vivo studies show that CpG DNA at high doses inhibits the re-stimulation and differentiation of FVIII-specific memory B cells. However, CpG DNA at low doses amplifies these processes. Amplification and inhibition of memory-B-cell responses are due to specific interactions of CpG DNA with TLR 9. Both effects are blocked by addition of a blocking agent for TLR 9 in vitro. We conclude that triggering of TLR 9 by bacterial DNA has a substantial influence on FVIII-specific memory-B-cell responses. The consequence of TLR 9 triggering can be inhibitory or stimulatory, depending on the actual concentration of the bacterial DNA. Our findings demonstrate the potential modulatory effects of bacterial infections on the regulation of FVIII inhibitor development.

scholarly journals In Vivo Generated Th1 Cells Can Migrate to B Cell Follicles to Support B Cell Responses

2004 ◽  
Vol 173 (3) ◽  
pp. 1640-1646 ◽  
Author(s):  
Karen M. Smith ◽  
James M. Brewer ◽  
Catherine M. Rush ◽  
Jillian Riley ◽  
Paul Garside
Keyword(s):  
B Cell ◽  
Th1 Cells ◽  
Cell Responses ◽  
B Cell Responses

scholarly journals High-Resolution Definition of Vaccine-Elicited B Cell Responses Against the HIV Primary Receptor Binding Site

2012 ◽  
Vol 4 (142) ◽  
pp. 142ra96-142ra96 ◽  
Author(s):  
C. Sundling ◽  
Y. Li ◽  
N. Huynh ◽  
C. Poulsen ◽  
R. Wilson ◽  
...  
Keyword(s):  
High Resolution ◽  
B Cell ◽  
Binding Site ◽  
Receptor Binding ◽  
Receptor Binding Site ◽  
Cell Responses ◽  
Primary Receptor ◽  
B Cell Responses ◽  
Definition Of

scholarly journals Ligation of CD27 on B Cells In Vivo during Primary Immunization Enhances Commitment to Memory B Cell Responses

2003 ◽  
Vol 171 (11) ◽  
pp. 5876-5881 ◽  
Author(s):  
Vanitha S. Raman ◽  
Rama S. Akondy ◽  
Satyajit Rath ◽  
Vineeta Bal ◽  
Anna George
Keyword(s):  
B Cells ◽  
B Cell ◽  
Primary Immunization ◽  
Memory B Cell ◽  
Cell Responses ◽  
B Cell Responses

scholarly journals Exposure of a Distinct PDCA-1+ (CD317) B Cell Population to Agonistic Anti-4-1BB (CD137) Inhibits T and B Cell Responses Both In Vitro and In Vivo

PLoS ONE ◽  
2012 ◽  
Vol 7 (11) ◽  
pp. e50272 ◽  
Author(s):  
Dass S. Vinay ◽  
Seung J. Lee ◽  
Chang H. Kim ◽  
Ho Sik Oh ◽  
Byoung S. Kwon
Keyword(s):  
B Cell ◽  
Cell Population ◽  
Cell Responses ◽  
B Cell Responses

In vivo control of B-cell survival and antigen-specific B-cell responses

2010 ◽  
Vol 237 (1) ◽  
pp. 90-103 ◽  
Author(s):  
Tyani D. Chan ◽  
Sandra Gardam ◽  
Dominique Gatto ◽  
Vivian M. Turner ◽  
John Silke ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Survival ◽  
Cell Responses ◽  
B Cell Survival ◽  
B Cell Responses

Bacterial cell wall-expressed protein A triggers supraclonal B-cell responses upon in vivo infection with Staphylococcus aureus

2005 ◽  
Vol 7 (15) ◽  
pp. 1501-1511 ◽  
Author(s):  
Niklas Palmqvist ◽  
Gregg J. Silverman ◽  
Elisabet Josefsson ◽  
Andrzej Tarkowski
Keyword(s):  
Staphylococcus Aureus ◽  
Cell Wall ◽  
B Cell ◽  
Bacterial Cell ◽  
Protein A ◽  
Bacterial Cell Wall ◽  
Cell Responses ◽  
B Cell Responses
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