Regulation of idiotype expression: II. THE PHENOTYPIC DIVERSITY OF T15 IDIOTYPE-BEARING ANTIBODY TO PHOSPHORYLCHOLINE IN RESPONSE TO T-DEPENDENT AND T-INDEPENDENT ANTIGENS.

The idiotypic (Id) diversity of the immune response to phosphorylcholine (PC) was studied by immunization of mice with thymus-dependent (PC-keyhole limpet haemocyanin; PC-KLH) and thymus-independent (S. pneumoniae R36a; Pn) forms of the antigen. Mice with the BALB/c genetic background (BALB/c, C.B20, and BALB.B) were used because their response to PC is dominated by immunoglobulins encoded in V_H-1 and V_k 22 genes, which uniformly express the T15 idiotype. The actual repertoire of the antibody was determined by idiotypic markers (Id) defined with monoclonal antibodies designated AB1–2, B36–82, MaId5–4, and B24–44. Previous studies from our laboratory have shown that these Id are present on TI5 (V_S107-1/V_k22) immunoglobulins only, but that they differentiate between somatic variants of the antibody molecules. We have measured the serum concentrations of these four Id after primary (1°), secondary (2°), and tertiary (3°) immunization; all of the Id activity was associated with the PC-binding antibody, as shown by specific immunoadsorbents. However, the levels of the Id-bearing (Id⁺) antibody did not correlate with each other. After immunization with PC-KLH, the AB1–2⁺ antibody declined precipitously, whereas the levels of B24–44 and B36–82 remained steady. A similar pattern of Id heterogeneity was seen at the level of direct antibody-plaque-forming cells from the spleen, suggesting that the idiotopic (clonal) diversification occurred already during the early IgM response. A significant portion of anti-PC antibody after the 3° PC-KLH immunization was negative for all four Id, implying that the late response to the antigen involved distinct, T15-negative clones. The same idiotope repertoire changes were observed in BALB/c and in congenic strains C.B20 (Ish^b) and BALB.B (H-2^b). A diversification of T15⁺ antibody was also detectable upon immunization with a T-independent antigen, Pn, but to a much lesser extent. These observations indicate that the T15⁺ antibody response in BALB/c mice is heterogeneous, and that there appears to be a selection of specific clonal variants in which the T cells play a role. [ABSTRACT FROM AUTHOR]