Mechanisms of idiotype suppression. II. Requirement of specific antigen for B cell inactivation by anti-idiotype antibody

Specific tolerance of BALB/c spleen cells to phosphorylcholine (PC) was induced in vitro by treatment with antibodies specific for the idiotype of TEPC-15 myeloma protein (anti-T15id) and a PC-containing antigen, R36a. The presence of anti-T15id antibody for at least 2 days was necessary to achieve a full level of suppression (> 98%) of anti-PC production in the presence of R36a. The anti-PC response of a nylon wool-separated B cell population was also greatly suppressed (94%) only after a 48-hr treatment with anti-T15id antibody plus antigen. In contrast, either isolated B or unseparated spleen cells treated with anti-T15id alone (without antigen) were fully responsive to PC. Kinetic studies indicated that treatment of cells with anti-T15id antibodies either in the presence or absence of R36a resulted in a gradual suppression of anti-PC responses at a similar rate during an initial 12-hr period. However, further treatment (24 hr) of cells with anti-T15id antibody alone led to recovery of anti-PC response from the suppression, whereas incubation with the anti-idiotype antibody plus R36a induced further suppression. These results indicate that anti-idiotype antibodies can directly inactivate B cells, and this inactivation becomes irreversible only after a continuous exposure to the antibodies in the presence of specific antigen.