Histocompatibility requirements for T cell help in specific in vitro antibody responses to influenza virus by human...

Specific antibody responses to influenza virus were obtained in vitro from human blood mononuclear cells (PBM). The response was T cell-dependent, as shown by separation of PBM into E rosette-positive (E+) and -negative (E-) populations. The histocompatibility requirements for T-B cells interactions in this response were analyzed by recombining E- and E+ fractions from donors with varying degrees of HLA compatibility. No antibody formation was obtained from any allogeneic combination except for the special case of HLA identical siblings. As these experiments included combinations with shared or identical HLA-DR specificities, it was unlikely that genetic restriction alone could account for the failure of T-B cell collaboration. Evidence that suppression was responsible for the lack of antibody formation was obtained from experiments in which allogeneic E+ cells profoundly depressed specific antibody responses of intact PBM. In contrast, no such suppression was seen in pokeweed mitogen-driven polyclonal Ig synthesis for which there are no major histocompatibility complex requirements for T cell help. The suppressor activity of allogeneic E+ cells was found to be radiation-sensitive. By irradiating E+ cells, it was, therefore, possible to test for T cell help across an HLA barrier without unwanted suppressor effects. Under these conditions, (irradiated) E+ cells were able to collaborate with allogeneic E- cells even with no HLA alleles in common. This was true even when autologous monocytes were depleted from the helper E+ population. Supernatants collected from antigen-driven cultures of allogeneic E- and E+ cells were able to replace helper T cells in the specific antibody response to influenza virus. The apparent lack of genetic restriction in these responses might, therefore, be explained by the production of a nonrestricted helper factor.