Potent differentiation-inducing properties of the antiretroviral agent 9-(2-phosphonylmethoxyethyl) adenine (PMEA) in the rat choriocarcinoma (RCHO) tumor cell model

We have compared the splenic responses following immunization with the T cell-independent (TI)-2 antigen native dextran B512 and with a thymus-dependent (TD) protein-dextran conjugate. Interestingly, primary immunization with native dextran induced germinal center (GC) formation in the spleen to the same extent as the protein-dextran conjugate. The GC were antigen-specific as characterized by the presence of peanut agglutinin (PNA)-positive areas that were also binding FITC-conjugated dextran. Dextran-binding B cells were also detected outside the GC as sites of antibody-producing cells. The secondary splenic response to native dextran was suppressed compared to the primary response, with almost no dextran-specific GC or extra-follicular sites with dextran-specific B cells present in the sections. This suppression could be reverted by using cholera toxin (CT) as an adjuvant for the dextran immunizations. Following native dextran immunization with CT adjuvant a secondary splenic GC response similar to a TD secondary splenic GC response was generated, with almost all the dextran-specific B cells located in the GC. Collectively, this indicates that the difference between TI and TD antigen responses is not due to different abilities in inducing GC development, rather the GC reaction is less productive for a TI antigen than for a TD antigen. CT can both increase secondary GC formation in particular for the TI form of dextran and ameliorate the GC reaction, as reflected by increased anti-dextran antibody levels.