Regulation of the humoral immune response: from immunoglobulin genes to regulatory T cell networks.

Leukemic lymphocytes were used in studies to define the rearrangements of immunoglobulin genes and the networks of immunoregulatory T cells that are important to the control of immunoglobulin synthesis in humans. Leukemic B cells displayed rearrangements of their expressed mu and k or lambda genes. Surprisingly, the k constant region genes were deleted or rearranged in all lambda-expressing B lymphocytes examined. Most non-T, non-B lymphocytic leukemias had immunoglobulin gene rearrangements, which indicates that these cells were committed to B cell development at the immunoglobulin gene level. The pattern of immunoglobulin gene rearrangements in the B cell precursor and B cell leukemias suggests an ordered hierarchy of somatic rearrangements with mu genes preceding light chains and k light chain genes preceding lambda. Some of the leukemic T cells studied were homogeneous populations of cells that retained immunoregulatory functions with many Sézary T leukemic cells functioning as helper cells in their interactions with B lymphocytes. In contrast, malignant cells from patients with the adult T leukemia of Japan frequently functioned as suppressor cells. In contrast to normal unactivated T cells or other leukemic T cells, the leukemic T cells from all adult T cell leukemia patients studied had an activated receptor for T cell growth factor. The malignant cells of a patient with an acute T cell leukemia functioned as prosuppressor cells. Under the influence of normal T cells or their secreted inducer products, these leukemic cells matured both functionally and in terms of cell surface antigens into suppressor effector cells.