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We have deliberately targeted collaboration between T cells and certain B cells by using a heteroconjugate (HETCONJ) antibody. This specific reagent was created by cross-linking the F(ab')2 portions of and-I-Ab and ant)-CD3 monoclonal antibodies. Spleen cells from B6 (I-Ab) but not bm 12 (I-A'bm12) mice proliferated in vitro in the presence of the HETCONJ. Similarly. T-cell dependent IgM secretion was induced in B cells from B6, yet only weakly in B cells from bm12 mice. Using B cells from Igh allotype double congenic (B6.C20 Igha/I-Ab and bm12, Ighb/I-Abm12) mice in co-culture experiments, we have used the HETCONJ to study linked versus bystander T--B interaction. B-cell activation, mediated by HETCONJ, was 10 times greater in unseparated than in resting splenic B cells. T--B interaction through T--B contact was more efficient than activation through bystander effects both for unseparated and resting splenic B cells. Large, already activated B cells, in contrast, did not show a preference for linked recognition. Our reagent has mimicked some of the events involved in T--B collaboration and may be useful in studying the molecular basis of cellular interactions. [ABSTRACT FROM AUTHOR]