A functional idiotypic network of T helper cells and antibodies, limited to the compartment of "naturally" activated lymphocytes in normal mice.

As shown previously, idiotype (Id) sharing between anti-2,4,6-trinitrophenyl T helper (Th) cells and antibodies in BALB/c mice results from immunoglobulin (Ig)-dependent selection of the T cell repertoire. In contrast, a clonotype defined by the same F6(51) anti-Id antibody is expressed by C57BL/6 anti-(4-hydroxy-3-nitrophenyl)acetyl Th cells independently of Ig influences. We have now used these systems to test the hypothesis that Ig-dependent Th cell repertoire selection occurs in the compartment of "naturally" activated lymphocytes. "Naturally" activated or resting splenic L3T4+ cells were separated from normal BALB/c and C57BL/6 mice and tested, either directly or after in vitro priming, in hapten-specific helper assays for expression of the clonotope defined by the F6(51) anti-Id antibody. The results show the selective expression of the antibody-dependent T cell Id in the "naturally" activated helper cell compartment. In contrast, when the T cell Id is expressed in the absence of Ig-dependent selection, it is only detected in the resting helper cell repertoire. Furthermore, BALB/c "natural" IgM antibodies with anti-Id specificities similar to F6(51) show functionally relevant interactions with syngeneic "naturally" activated Th cells. These are also characterized by high paratopic/Id degeneracy, as compared to helper cells obtained by conventional immunization. These results demonstrate repertoire differences between the set of (resting) lymphocytes participating in immune responses, vs. those "internally" activated in normal individuals. They also suggest the importance of Id network interactions in the compartment of "naturally" activated T and B cells.