TLR4 and TRIF-dependent stimulation of B lymphocytes by peptide liposomes enables T-cell independent isotype switch in mice

Pihlgren, Maria, Silva, Alberto B., Madani, Rime, Giriens, Valerie, Waeckerle-Men, Ying, Fettelschoss, Antonia, Hickman, David T., López-Deber, María Pilar, Mlaki Ndao, Dorin, Vukicevic, Marija, Buccarello, Anna Lucia, Gafner, Valerie, Chuard, Nathalie, Reis, Pedro, Piorkowska, Kasia, Pfeifer, Andrea, Kündig, Thomas M., Muhs, Andreas and Johansen, Pål (2012) TLR4 and TRIF-dependent stimulation of B lymphocytes by peptide liposomes enables T-cell independent isotype switch in mice. Blood, 121 1: 85-94. doi:10.1182/blood-2012-02-413831


Author Pihlgren, Maria
Silva, Alberto B.
Madani, Rime
Giriens, Valerie
Waeckerle-Men, Ying
Fettelschoss, Antonia
Hickman, David T.
López-Deber, María Pilar
Mlaki Ndao, Dorin
Vukicevic, Marija
Buccarello, Anna Lucia
Gafner, Valerie
Chuard, Nathalie
Reis, Pedro
Piorkowska, Kasia
Pfeifer, Andrea
Kündig, Thomas M.
Muhs, Andreas
Johansen, Pål
Title TLR4 and TRIF-dependent stimulation of B lymphocytes by peptide liposomes enables T-cell independent isotype switch in mice
Journal name Blood   Check publisher's open access policy
ISSN 0006-4971
1528-0020
Publication date 2012-11-08
Sub-type Article (original research)
DOI 10.1182/blood-2012-02-413831
Volume 121
Issue 1
Start page 85
End page 94
Total pages 10
Place of publication Washington, DC, United States
Publisher American Society of Hematology
Collection year 2013
Language eng
Abstract Immunoglobulin class switching from IgM to IgG in response to peptides is generally T cell–dependent and vaccination in T cell–deficient individuals is inefficient. We show that a vaccine consisting of a dense array of peptides on liposomes induced peptide-specific IgG responses totally independent of T-cell help. Independency was confirmed in mice lacking T cells and in mice deficient for MHC class II, CD40L, and CD28. The IgG titers were high, long-lived, and comparable with titers obtained in wild-type animals, and the antibody response was associated with germinal center formation, expression of activation-induced cytidine deaminase, and affinity maturation. The T cell–independent (TI) IgG response was strictly dependent on ligation of TLR4 receptors on B cells, and concomitant TLR4 and cognate B-cell receptor stimulation was required on a single-cell level. Surprisingly, the IgG class switch was mediated by TIR-domain-containing adapter inducing interferon-β (TRIF), but not by MyD88. This study demonstrates that peptides can induce TI isotype switching when antigen and TLR ligand are assembled and appropriately presented directly to B lymphocytes. A TI vaccine could enable efficient prophylactic and therapeutic vaccination of patients with T-cell deficiencies and find application in diseases where induction of T-cell responses contraindicates vaccination, for example, in Alzheimer disease.
Keyword Vaccine
T cell–deficient
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Non HERDC
Institute for Molecular Bioscience - Publications
 
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Created: Fri, 04 Jan 2013, 11:10:29 EST by Alberto Boucas Da Silva on behalf of Institute for Molecular Bioscience