The expression of Fc receptors (FcR) for IgA (Fc alpha R) as well as for IgE (Fc epsilon R) on T lymphocytes (T cells) is enhanced or up regulated by the corresponding class of immunoglobulins (Ig). The production of class-specific regulatory factors binding to IgA and IgE (IgA binding factor [IgA-BF]; IgE binding factor [IgE-BF]) is also induced by these respective ligands. Murine IgA-BFs produced by a T hybridoma T2D4 and concanavalin A-activated spleen cells suppressed the in vitro IgA antibody responses of pokeweed mitogen-stimulated mouse spleen cells class-specifically. Human IgA antibody response was also suppressed by the murine IgA-BF. Similar suppressive IgA-BF is also produced by a human natural killer (NK)-like cell line (YT), which has no rearrangement of the T cell receptor beta-chain gene, indicating that non-T non-B/LGL cells may also be involved in the regulation of the class-specific antibody responses. It appears that, in human as well as murine systems, T- and NK-cells have the capacity to co-express multiple class-specific FcRs and to produce the corresponding immunoglobulin binding factors. While the Fc epsilon R expression is abnormally enhanced in the diseases with hyperimmunoglobulinemia E, disregulation of Fc alpha R is associated with certain human diseases involving the altered IgA regulation. In IgA nephropathy, which is characterized by increased serum IgA level and IgA deposition in the mesangium, there is an enhancement of the expression of Fc alpha R. In contrast, IgA failed to induce Fc alpha R significantly on the lymphocytes from the patients with selective IgA deficiency, indicating that Fc alpha R plays an important role in the IgA regulation in vivo.