B CELL, HELPER T CELL, AND SUPPRESSOR T CELL ABNORMALITIES CONTRIBUTE TO DISORDERED IMMUNOGLOBULIN SYNTHESIS IN PATIENTS FOLLOWING BONE MARROW TRANSPLANTATION

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Abstract
The pathogenic mechanisms responsible for hypogammaglobulinemia that occurs in patients who have undergone bone marrow transplantation were studied using peripheral blood lymphocytes in an in vitro Ig biosynthesis assay. None of the 9 marrow recipients between 2-15 mo. after transplantation produced normal amounts of IgG, IgA or IgM in response to pokeweed mitogen (a T cell-dependent activator). Three of these same patients responded to Epstein-Barr virus (a helper T cell-independent activator), suggesting that these 3 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 5 cases. These suppressor cells frequently had profound activity (> 80% suppression of the Ig synthesis of cocultured normal cells), were predominantly radioresistant, and were T cells in the cases where analyzed. Helper T cell activity for Ig synthesis was not demonstrable in 7 of the 9 cases. 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, 2 patients had demonstrable helper T cell defects with partially responsive B cells and no excessive suppressor activity. These 2 patients were experiencing a recurrence of their hypogammaglobulinemia following a period of normalized Ig levels. Defects within all lymphocytic elements involved in the response and regulation of Ig synthesis were identified and may contribute to the humoral immunodeficiency which follows marrow transplantation.