Pattern Recognition by B Cells: The Role of Antigen Repetitiveness Versus Toll-Like Receptors
Viruses induce excellent antibody responses due to several intrinsic features. Their repetitive, organised structure is optimal for the activation of the B cell receptor (BCR), leading to an increased humoral response and a decreased dependence on T cell help. Viruses also trigger Toll-like receptors (TLRs), which in addition to increasing overall Ig levels, drive the switch to the IgG2a isotype. This isotype is more efficient in viral and bacterial clearance and will activate complement, which in turn lowers the threshold of BCR activation. Exploiting these characteristics in vaccine design may help us to create vaccines which are as safe as a recombinant vaccine yet still as effective as a virus in inducing B cell responses.
KeywordsVesicular Stomatitis Virus Epitope Density Antigen Organisation Antigen Repetitiveness High Epitope Density
B cell receptor
Red blood cell
Signal transducers and activators of transcription
Vesicular stomatitis virus
Glycoprotein of vesicular stomatitis virus
Unable to display preview. Download preview PDF.
- Ahearn JM, Fischer MB, Croix D, Goerg S, Ma M, Xia J, Zhou X, Howard RG, Rothstein TL, Carroll MC (1996) Disruption of the Cr2 locus results in a reduction in B-1a cells and in an impaired B cell response to T-dependent antigen Immunity 4:251–262.Google Scholar
- Ambuhl PM, Tissot AC, Fulurija A, Maurer P, Nussberger J, Sabat R, Nief V, Schellekens C, Sladko K, Roubicek K, Pfister T, Rettenbacher M, Volk HD, Wagner F, Muller P, Jennings GT, Bachmann MF (2007) A vaccine for hypertension based on virus-like particles: preclinical efficacy and phase I safety and immunogenicity J Hypertens 25:63–72.PubMedCrossRefGoogle Scholar
- Jegerlehner A, Tissot A, Lechner F, Sebbel P, Erdmann I, Kundig T, Bachi T, Storni T, Jennings G, Pumpens P, Renner WA, Bachmann MF (2002b) A molecular assembly system that renders antigens of choice highly repetitive for induction of protective B cell responses. Vaccine 20:3104–3112.PubMedCrossRefGoogle Scholar
- MMWR (1986) Update: influenza activity–United States. MMWR Morb Mortal Wkly Rep 35:249–251.Google Scholar
- Nemazee D, Gavin A, Hoebe K, Beutler B (2006) Immunology: Toll-like receptors and antibody responses. Nature 441:E4; discussion E4.Google Scholar
- Peng SL, Li J, Lin L, Gerth A (2003) The role of T-bet in B cells. Nat Immunol 4:1041; author reply 1041.Google Scholar
- Van den Eertwegh AJ, Noelle RJ, Roy M, Shepherd DM, Aruffo A, Ledbetter JA, Boersma WJ, Claassen E (1993) In vivo CD40-gp39 interactions are essential for thymus-dependent humoral immunity. I. In vivo expression of CD40 ligand, cytokines, and antibody production delineates sites of cognate T-B cell interactions. J Exp Med 178:1555–1565.PubMedCrossRefGoogle Scholar