B cell, helper T cell, and suppressor T cell abnormalities contribute to disordered immunoglobulin synthesis in patients following bone marrow transplantation.

The pathogenic mechanisms responsible for the hypogammaglobulinemia that occurs in patients who have undergone bone marrow transplantation were studied using peripheral blood lymphocytes in an in vitro immunoglobulin biosynthesis assay. None of the nine marrow recipients between 2 and 15 months after transplantation produced normal amounts of IgG, IgA, or IgM in response to pokeweed mitogen (a T cell-dependent activator). However, three of these same patients responded to Epstein-Barr virus (a helper T cell- independent activator), suggesting that these three possessed responsive B cells. Cocultures of the marrow recipients' lymphocytes with lymphocytes from their respective donors or other normal subjects documented excessive suppressor cell activity in five cases. These suppressor cells frequently had profound activity (greater than 80% suppression of the immunoglobulin synthesis of cocultured normal cells), were predominantly radioresistant, and were T cells in the cases where analyzed. Helper T cell activity for immunoglobulin synthesis was not demonstrable in seven of the nine cases. In addition, four of the patients apparently possessed defective B cells. Although most patients had combined defects of several lymphocyte subpopulations, it appeared that either an isolated helper T cell or isolated B cell deficiency was sufficient to result in altered Ig synthesis. In this regard, two patients had demonstrable helper T cell defects with partially responsive B cells and no excessive suppressor activity. Interestingly, these two patients were experiencing a recurrence of their hypogammaglobulinemia following a period of normalized immunoglobulin levels. Thus, defects within all lymphocytic elements involved in the response and regulation of immunoglobulin synthesis were identified and may contribute to the humoral immunodeficiency which follows marrow transplantation.