Distinct functional phenotypes of cloned Ia-restricted helper T cells.

Analysis of activation of phosphorylcholine (PC)-specific B cells by a large number of different cloned, self Ia-specific helper T cell (Th) clones has permitted the classification of such T cells into four distinct functional types. Types 1 and 2 induce B cells to secrete anti-PC antibody in an antigen-specific, Ia-restricted fashion. Type 3 cells induce antigen-specific, Ia-restricted B cell proliferation, but do not lead to specific antibody formation, and have been shown previously to have suppressor functions. Type 4 cells are autoreactive, and induce antigen-independent B cell activation and antibody secretion. The distinction between type 1 and type 2 Th clones was analyzed in detail. In bulk cultures, type 1 cloned lines generate an idiotypically heterogeneous anti-PC antibody response, whereas type 2 cloned lines induce a larger response that is dominated by the T15 idiotype. In limiting-dilution analyses, type 2 cells induce fourfold more T15+, PC-specific precursor B cells than do type 1 cells, and in addition, induce larger burst sizes for T15+, PC-specific B cells. Type 4 clones can also be subdivided into cells that are type 1-like, and cells that are type 2-like. These differences in functional phenotype are seen over a broad range of antigen and cell doses. Detailed analysis of the behavior of these distinct functional types of Th should allow a better understanding of the functional properties of mixed populations of antigen-primed, Ia-restricted Th cells.