Journal Article

Inhibition of antibody production <i>in vivo</i> by pre-stimulation of Toll-like receptor 4 before antigen priming is caused by defective B-cell priming and not impairment in antigen presentation

Nurlaely Mida Rachmawati, Kenji Fukudome, Naoko Tsuneyoshi, Uleng Bahrun, Hiroki Tsukamoto, Tsutomu Yanagibashi, Yoshinori Nagai, Kiyoshi Takatsu, Shoichiro Ohta and Masao Kimoto

in International Immunology

Volume 25, issue 2, pages 117-128
Published in print February 2013 | ISSN: 0953-8178
Published online October 2012 | e-ISSN: 1460-2377 | DOI: http://dx.doi.org/10.1093/intimm/dxs096
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

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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.

Keywords: agonistic monoclonal antibody; endotoxin tolerance; innate immunity; LPS

Journal Article.  6695 words.  Illustrated.

Subjects: Immunology ; Biological Sciences

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