Murine immune response to Neisseria meningitidis group C capsular polysaccharide: Analysis of monoclonal antibodies generated in response to a thymus-independent antigen and a thymus-dependent toxoid conjugate vaccine

Antibody (Ab) responses to polysaccharides (PSs) such as Neisseria meningit idis group C PS (MCPS) are characterized as being thymus independent (TI) a nd are restricted with regard to clonotype and isotype expression. PS conju gated to proteins, e.g., MCPS coupled to tetanus toroid (MCPS-TT), elicits a thymus-dependent (TD) response. In order to understand the influence of t he form of a vaccine (TI versus TD) on the Ab repertoire, we generated mono clonal antibody (MAb) panels from mice immunized and boosted with MCPS or M CPS-TT in different ways. The panels of MAbs were examined for isotype, fin e specificity, affinity, and V-H gene family usage. The use of MCPS-TT resu lted in a shift in the isotype from immunoglobulin M (IgM) and IgG3 elicite d in response to the MCPS to primarily IgG1. This isotype shift was accompa nied by a change in the fine specificity of the response to the conjugate c ompared to that of PS. New fine specificities and increased affinity were o bserved in response to the TD antigen (Ag). Dot blot and Northern analyses of MCPS MAbs revealed that V-H gene family usage is dominated by V(H)J558, used by 23 of 39 MAbs. V(H)3609 was seen in three MAbs of restricted fine s pecificity. V(H)Q52, V(H)7183, and V(H)VGAM3-8 were seen in more than one M Ab across these panels, while V(H)10 and V(H)X24 were detected only once in response to the TI-2 Ag. All MAbs in the panels utilized kappa light chain s, and all functional J(kappa) genes were expressed.