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

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.

journal_name

Blood

journal_title

Blood

authors

Pihlgren M,Silva AB,Madani R,Giriens V,Waeckerle-Men Y,Fettelschoss A,Hickman DT,López-Deber MP,Ndao DM,Vukicevic M,Buccarello AL,Gafner V,Chuard N,Reis P,Piorkowska K,Pfeifer A,Kündig TM,Muhs A,Johansen P

doi

10.1182/blood-2012-02-413831

subject

Has Abstract

pub_date

2013-01-03 00:00:00

pages

85-94

issue

1

eissn

0006-4971

issn

1528-0020

pii

blood-2012-02-413831

journal_volume

121

pub_type

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