Igh-lb-specific CD4+CD8-T cell clones of the Thl subset selectively suppress the Igh-lb allotype in vivo*
The demonstration of major histocompatibility complex (MHC)-restricted T helper (Th) cells specific for peptides from the variable (V) regions of syngeneic immunoglobulin (Ig) (idiopeptides) opens the possibility that Th cells regulate B cell functions via idiopeptide-based cognate T-B interactions. As a model for such interactions we investigated the influence of Ig allotype-specific T cells on the differentiation of H-Zsyngeneic B cells expressing that particular Ig allotype. We established a BALB/c (H-2d, Iga) CD4+CD8-Tcell line and clones Of theTh1 subset (interleukin 2+, interleukin 4-, interferon-y+, tumor necrosis factor-a+) that recognized Igh-1 (IgG2,) of the b allotype (Igh-lb) together with I-Ad.These T cells specifically suppressed surface Igh-lb+ B cells in vitro and in vivo. In 12 out of 15 6-week-old (BALB/c x BlO.D2)Fl mice neonatally injected with Ighlb-specificTcells, the serum Igh-lb concentrations were < 5% of the levels in the controls. Thus, allotype suppression can be accomplished solely by adoptive transfer of Igh-lb-specific CD4+ Tcells. The in vivo suppression was specific for Igh-lb+ B cells as the recipients' levels of Igh-la and Igh4b (IgGlb) were unaffected. The Vpl4-specific anti-T cell receptor (TcR) monoclonal antibody 14-2 inhibited activation of hybridomas derived from two of the clones. Collectively the data indicate that suppression resulted from cognate interactions between allopeptide-specific TcR a@+ T cells and normal unmanipulated B lymphocytes presenting their endogenous Igh-lb in association with MHC class I1 molecules.The data support the possibility that normal B cells can be suppressed by idiopeptide-specific T cells in vivo.