PMID- 25053813
OWN - NLM
STAT- MEDLINE
DCOM- 20141003
LR  - 20211021
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Print)
IS  - 0027-8424 (Linking)
VI  - 111
IP  - 31
DP  - 2014 Aug 5
TI  - Toll-like receptor 9 signaling acts on multiple elements of the germinal center 
      to enhance antibody responses.
PG  - E3224-33
LID - 10.1073/pnas.1323985111 [doi]
AB  - Recent studies have demonstrated important roles of nucleic acid-sensing 
      Toll-like receptors (TLRs) in promoting protective antibody responses against 
      several viruses. To dissect how recognition of nucleic acids by TLRs enhances 
      germinal center (GC) responses, mice selectively deleted for myeloid 
      differentiation primary-response protein 88 (MyD88) in B cells or dendritic cells 
      (DCs) were immunized with a haptenated protein antigen bound to a TLR9 ligand. 
      TLR9 signaling in DCs led to greater numbers of follicular helper T (TFH) cells 
      and GC B cells, and accelerated production of broad-affinity antihapten IgG. In 
      addition to modulating GC selection by increasing inducible costimulator (ICOS) 
      expression on TFH cells and reducing the number of follicular regulatory T cells, 
      MyD88-dependent signaling in B cells enhanced GC output by augmenting a class 
      switch to IgG2a, affinity maturation, and the memory antibody response. Thus, 
      attachment of a TLR9 ligand to an oligovalent antigen acted on DCs and B cells to 
      coordinate changes in the T-cell compartment and also promoted B cell-intrinsic 
      effects that ultimately programmed a more potent GC response.
FAU - Rookhuizen, Derek C
AU  - Rookhuizen DC
AD  - Department of Molecular and Cell Biology, Life Sciences Addition, University of 
      California, Berkeley, CA 94720; and.
FAU - DeFranco, Anthony L
AU  - DeFranco AL
AD  - Department of Microbiology and Immunology, University of California, San 
      Francisco, CA 94143 anthony.defranco@ucsf.edu.
LA  - eng
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20140722
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (Forkhead Transcription Factors)
RN  - 0 (Foxp3 protein, mouse)
RN  - 0 (Haptens)
RN  - 0 (Ligands)
RN  - 0 (Myeloid Differentiation Factor 88)
RN  - 0 (Nitrophenols)
RN  - 0 (Tlr9 protein, mouse)
RN  - 0 (Toll-Like Receptor 9)
RN  - 0 (gamma-Globulins)
SB  - IM
MH  - Animals
MH  - Antibody Affinity/drug effects
MH  - Antibody Formation/drug effects/*immunology
MH  - B-Lymphocytes/drug effects/immunology
MH  - Chickens
MH  - Dendritic Cells/drug effects/immunology
MH  - Forkhead Transcription Factors/metabolism
MH  - Germinal Center/*immunology
MH  - Haptens/pharmacology
MH  - Immunologic Memory/drug effects
MH  - Ligands
MH  - Lymphocyte Activation/drug effects
MH  - Lymphocyte Count
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Myeloid Differentiation Factor 88/metabolism
MH  - Nitrophenols/pharmacology
MH  - Phenotype
MH  - Signal Transduction/*immunology
MH  - Toll-Like Receptor 9/*metabolism
MH  - gamma-Globulins/pharmacology
PMC - PMC4128120
COIS- The authors declare no conflict of interest.
EDAT- 2014/07/24 06:00
MHDA- 2014/10/04 06:00
PMCR- 2015/02/05
CRDT- 2014/07/24 06:00
PHST- 2014/07/24 06:00 [entrez]
PHST- 2014/07/24 06:00 [pubmed]
PHST- 2014/10/04 06:00 [medline]
PHST- 2015/02/05 00:00 [pmc-release]
AID - 1323985111 [pii]
AID - 201323985 [pii]
AID - 10.1073/pnas.1323985111 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 2014 Aug 5;111(31):E3224-33. doi: 
      10.1073/pnas.1323985111. Epub 2014 Jul 22.