INDUCTION OF B-CELL APOPTOSIS BY THO, BUT NOT TH2, CD4(-CELLS() T)

Engagement of the T cell receptor molecules with MHC-antigen complexes presented by B cells ascertains antigen specificity in T cell-depende nt help. Ligation of MHC molecules on the surface of B cells, however, has not only been implicated in antigen-specific T-B cell interaction , but has also been linked to the induction of B cell apoptosis. To ex amine the role of T helper cells in either induction of immunoglobulin synthesis or B cell apoptotic death, we have facilitated T cell recep tor-MHC interaction through a bacterial superantigen. CD4(+) T cell cl ones could be categorized into two clearly distinct subsets based upon their ability to promote B cell help in the presence of superantigen. One subset of T cell clones supported immunoglobulin synthesis, and t hus functioned as effective helper cells. B cells interacting with the second subset of T cells did not differentiate into antibody-secretin g cells, but underwent apoptosis. Both types of helper cells were able to provide contact help after anti-CD3 stimulation. Induction of apop tosis was a dominant phenomenon; the addition of the superantigen supp ressed immunoglobulin production in B cells activated by anti-CD3-stim ulated helper T cells, indicating that the T cells delivered an apopto tic signal to the B cell. T cell clones providing effective MHC restri ctive B cell help could be distinguished from T cells facilitating B c ell apoptosis based on their lymphokine secretion profile. Induction o f B cell apoptosis was a feature of T cells with a THO lymphokine patt ern. Promotion of MHC-restricted B cell help was associated with a TH2 lymphokine profile. TH1-derived cytokines alone could not substitute for apoptosis-inducing T cells.