Inhibition of antibody production in vivo by pre-stimulation of Toll-like receptor 4 before antigen priming is caused by defective B-cell priming and not impairment in antigen presentation.
Rachmawati, Nurlaely Mida 1; Fukudome, Kenji 1; Tsuneyoshi, Naoko 1; Bahrun, Uleng 1 , 6; Tsukamoto, Hiroki 1 , 2; Yanagibashi, Tsutomu 3; Nagai, Yoshinori 3; Takatsu, Kiyoshi 3 , 4; Ohta, Shoichiro 5; Kimoto, Masao 1
[Article] International Immunology. 25(2):117-128, February 2013.

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Stimulation of Toll-like receptor 4 (TLR4) induces not only innate but also adaptive immune responses, and has been suggested to exert adjuvant effects. Additional to such positive effects, pre-stimulation of TLR4 induces endotoxin tolerance where animals are unresponsive to subsequent lethal challenges with lipopolysaccharide (LPS). We examined the effects of pre-stimulation of TLR4 using an agonistic anti-TLR4 mAb (UT12) on antibody production in vivo. Pre-injection of UT12 prior to both primary and secondary immunization completely inhibited antigen-specific antibody responses. Cellular analysis revealed that the inhibition was not due to impairment of T-cell activation. Accordingly, T-helper activities in UT12 pre-injected mice were not impaired. In contrast, B-cell priming was defective in UT12 pre-injected mice. The observation that the expression of activation markers such as CD69 and CD86 on B cells was blocked by UT12 pre-injection supports this. Interestingly, UT12 pre-injection only showed inhibitory effects at the primary and not the secondary immunization. These results provide important information concerning the regulatory mechanisms of antibody production, especially in endotoxin-tolerant states.

(C) The Japanese Society for Immunology 2013. Published by Oxford University Press. All rights reserved.