title: Regulation of IgG antibody responses by epitope density and CD21-mediated costimulation.
abstract: Epitope density and organization have been shown to be important factors for B cell activation in many animal model systems. However, it has been difficult to separate the role of antigen organization from the role of local antigen concentrations because highly organized antigens are usually particulate whereas non-organized antigens are more soluble. Hence, highly organized and non-organized antigens may interact with different cell types and in different locations within lymphoid organs. In order to assess the role of antigen organization in regulating B cell responses, we immunized mice with highly repetitive virus-like particles, which exhibit different epitope densities covalently attached to them. Therefore, the same particulate structure was used to present identical epitopes that differed in their degree of organization. Induction of epitope-specific IgM titers, reflecting early B cell activation, were unaffected by the degree of epitope density. Furthermore, the absence of Th cells or CD21/CD35 did not reduce the IgM response. In contrast, the degree of organization was a critical factor influencing the magnitude of the epitope-specific IgG response. Moreover, the threshold for IgG responses was shifted in the absence of CD21/CD35, resulting in the requirement for higher epitope densities to allow efficient IgG responses. Thus, IgG but not IgM responses are regulated by epitope density and B cell costimulatory thresholds.
authors.affiliation: Cytos Biotechnology AG, Schlieren, Switzerland.
authors.forename: Andrea
authors.initials: A
authors.lastname: Jegerlehner
authors.forename: Tazio
authors.initials: T
authors.lastname: Storni
authors.forename: Gerd
authors.initials: G
authors.lastname: Lipowsky
authors.forename: Markus
authors.initials: M
authors.lastname: Schmid
authors.forename: Paul
authors.initials: P
authors.lastname: Pumpens
authors.forename: Martin F
authors.initials: MF
authors.lastname: Bachmann
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D015703:Antigens, CD / Q000502:physiology; D001402:B-Lymphocytes / Q000276:immunology*; D000939:Epitopes; D005260:Female; D007074:Immunoglobulin G / Q000096:biosynthesis*; D007075:Immunoglobulin M / Q000096:biosynthesis; D008565:Membrane Proteins / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D017463:Receptors, Complement 3b / Q000502:physiology; D017464:Receptors, Complement 3d / Q000502:physiology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D060225:Tetraspanin 28; D014771:Virion / Q000276:immunology
chemical_list: D015703:Antigens, CD; C554799:Cd81 protein, mouse; D000939:Epitopes; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D008565:Membrane Proteins; D017463:Receptors, Complement 3b; D017464:Receptors, Complement 3d; D060225:Tetraspanin 28