Immunology: Toll-like receptors and antibody responses

Abstract

Microbial components, such as lipopolysaccharides, augment immune responses by activating Toll-like receptors (TLRs). Some have interpreted this to mean that TLR signalling might not only help to initiate the adaptive immune response, but may also be required for it. The expanded view is shared by Pasare and Medzhitov, who conclude from an analysis of mice deficient in MyD88 (a TLR-signalling adaptor protein) that the generation of T-dependent antigen-specific antibody responses requires activation of TLRs in B cells. However, we show here that robust antibody responses can be elicited even in the absence of TLR signals. This appreciable TLR-independence of immune responses should be taken into account in the rational design of immunogenic and toleragenic vaccines.

Figure 1. Antibody responses

T-cell-dependent antibody responses in wild-type C57BL/6 mice (yellow) and in MyD88^−/−/TRIF^Lps2/Lps2 double-knockout mice (red), which lack Toll-like-receptor activity. Young adult mice were given 100 µg endotoxin-free trinitrophenol–haemocyanin conjugates in alum. At day 7 post-immunization, serum antibody responses of the antibody isotypes IgM, IgG1, IgG2c, IgG2b and IgG3 were quantified by using an enzyme-linked immunosorbent assay, with titres representing the dilution giving half-maximal optical density. Means and standard errors are shown for six mice per group. Sera from unimmunized C57BL/6 mice (blue) establish the background of the assay.