In vitro and in vivo regulation of immunoglobulin synthesis
A series of cells and antibody proteins make up a critically important system of immunity. This immunological system, when functioning adequately, protects us against infections by bacterial, parasitic, viral and fungal agents, and even against the growth of cancer cells. When the system does not function normally, we are plagued by a wide array of diseases. One of the fundamental questions in the field of immunology is how the immune system recognises up to 100 million substances as foreign, yet normally does not direct its attack against the tissues of the individual. Over the past few years there have been enormous advances in our understanding of how the human immune system is regulated. A number of these insights have emerged from the study of neoplasms of the B cell/plasma cell and of the T cell series. For example, the recognition that paraproteins derived from patients with multiple myeloma, represent homogeneous unmunoglobulins was an indispensable step in understanding the structural and functional aspects of immunoglobulin molecules. In this chapter I shall focus on studies of leukaemic B and T lymphocytes which were directed towards defining the molecular events and cellular interactions that control immunoglobulin synthesis. In the first section I shall discuss studies applying the techniques of molecular biology to lymphoid cells which were directed towards defining the early events in the differentiation of stem cells into B cells. In the second section I shall consider the terminal maturation of B cells into immunoglobulin-synthesising plasma cells. Here I shall focus on malignancies of T cell origin which are of exceptional interest because in certain cases they retain immunoregulatory properties and are useful in resolving questions concerning the regulatory network of cells that control B cell maturation and immunoglobulin production. In the final section I shall consider the physiological and pathophysiological factors that control the metabolism of immunoglobulin molecules and the abnormalities in immunoglobulin survival that lead to disorders of immunoglobulin levels in disease states.
KeywordsImmunoglobulin Gene Leukaemic Cell Primary Immunodeficiency Disease Sezary Syndrome Acute Lymphocytic Leukaemia
Unable to display preview. Download preview PDF.
- 1.Hieter, P. A., Max, E. E., Seidman, J. G., Maizel, J. V. and Leder, P. (1980). Cloned human and mouse kappa immunoglobulin constant and J region genes conserve homology in functional segments. Cell, 22, 197–207.Google Scholar
- 2.Hieter, P. A., Korsmeyer, S. J., Waldmann, T. A. and- Leder, P. (1981). Human immunoglobulin kappa light chain genes are deleted or rearranged in lambda producing B-cells. Nature, Lond., 290, 368–372.Google Scholar
- 10.Gershon, R. K. (1974). T cell control of antibody production. Contemp. Top. Immunol, 3, 1–40.Google Scholar
- 14.Broder, S., Poplack, D., Whang-Peng, J., Durm, M., Goldman, C.,, Muul, L. and Waldmann, T. A. (1978). Characterisation of a suppressor cell leukemia: Evidence for the requirement of an interaction of two T cells in the development of human suppressor effector cells. New Engl J. Med, 298, 66–72.Google Scholar
- 15.Waldmann, T. A. (1975). Protein losing gastroenteropathies. In Gastroenterology, 3rd edn ( H. L. Bockus, Ed.), Saunders, Philadelphia, pp. 361–385.Google Scholar
- 16.Waldmann, T. A. and Strober, W. (1969). Metabolism of immunoglobulins. Progr. Allergy, 13, 10–110.Google Scholar