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C Goldman

Publications and source records attributed to C Goldman.

42 records · Page 3Linked to original sources

The role of suppressor cells in the pathogenesis of common variable hypogammaglobulinemia and the immunodeficiency associated with myeloma.

The role of suppressor cells in the pathogenesis of immunodeficiency was analyzed using a technique that permits study of the differentiation of B lymphocytes into immunoglobulin-synthesizing plasma cells. Lymphocytes from normals synthesized 4,910 ng of IgM, 1,270 ng of IgA, and 1,625 ng of IgG per 2 X 10(6) cells when cultured for 7 days in the presence of pokeweed mitogen. In contrast the lymphocytes from patients with common variable hypogammaglobulinemia did not synthesize significant quantities of immunoglobulin. When lymphocytes from 9 of 13 patients with common variable hypogammaglobulinemia studied were cocultured with normal lymphocytes, the synthesis of immunoglobulin by the normal lymphocytes was depressed by 75-100%. A comparable suppression of immunoglobulin synthesis by normal lymphocytes was observed when they were cocultured with T cells from hypogammaglobulinemic patients. These studies suggest that in some patients the disease common variable hypogammaglobulinemia may not be due to an intrinsic defect of B cells alone but may be cuased or perpetuated by an abnormality of regulatory T cells that act to suppress B-cell maturation and antibody production. Peripheral blood lymphocytes from myeloma patients also had a drastically reduced capacity to produce polyclonal immunoglobulins. Three of 6 myeloma patients tested had circulating mononuclear cells that suppressed immunoglobulin production by cocultured normal lymphocytes. Purified T cells from myeloma patients did not mediate this suppressor effect. These observations suggest that one mechanism for the humoral immune deficiency observed in myeloma patients is a block of polyclonal B-cell maturation by suppressor cells.

Agammaglobulinemia↗

Defect in IgA secretion and in IgA specific suppressor cells in patients with selective IgA deficiency.

The nature of the defect in patients with selective IgA deficiency was investigated using a technique established to study terminal differentiation of B lymphocytes into immunoglobulin synthesizing and secreting cells. The peripheral blood lymphocytes from normal individuals had geometric mean synthetic rates of 4910 ng for IgM, 1625 ng for IgG and 1270 ng for IgA per 2 x 10(6) cells in culture for 7 days in the presence of pokeweed mitogen. The cultured lymphocytes from each of the 14 patients with selective IgA deficiency studied synthesized normal quantities of IgG and IgM but secreted less than 100 ng of IgA into the media. However, 11 of the 14 patients studied synthesized IgA by the 7th day in PWM stimulated cultures as assessed by staining for cytoplasmic IgA using fluorescein-labeled anti-IgA antisera. Synthesis and secretion of IgA by normal cells was not suppressed when they were co-cultured with lymphocytes from these patients that synthesize but do not secrete IgA. Three of the 14 patients did not have lymphocytes with IgA demonstrable in their cytoplasm following culture. When the lymphocytes from these 3 patients were co-cultured with normal lymphocytes and pokeweed mitogen the synthesis of IgA by the normal cells was depressed by 80 to 100%. Synthesis of IgG and IgM was not depressed. These studies suggest that lymphocytes cultured with pokeweed mitogen from the majority of patients with selective IgA deficiency can synthesize IgA but have a defect in IgA secretion. A smaller group of the patients do not synthesize IgA and have IgA specific suppressor cells that prevent B cells from maturing into IgA synthesizing and secreting cells.

Adolescent↗

Impaired synthesis of polyclonal (non-paraprotein) immunoglobulins by circulating lymphocytes from patients with multiple myeloma Role of suppressor cells.

Since patients with myeloma have serious abnormalities of humoral immunity, we applied an in vitro assay to determine the capacity of B lymphocytes to mature into immunoglobulin-secreting cells. In peripheral blood lymphocytes from 22 normal persons, geometric mean immunoglobulin synthesis was 4910 ng for IgM, 1270 ng for IgA and 1625 ng for IgG. The synthesis rates of peripheral blood lymphocytes of 22 patients with myeloma were 458 ng for IgM, 321 ng for IgA and 218 ng for IgG. Circulating mononuclear cells from three of six patients tested suppressed polyclonal immunoglobulin synthesis by cocultured normal lymphocytes. Suppressive activity was not mediated by purified T cells alone. Removal of phagocytic mononuclear cells from lymphocyte populations of one patient nullified suppressive activity. Removal of phagocytic mononuclear cells from lymphocyte populations of a second patient led to a nearly 10-fold increase in polyclonal immunoglobulin synthesis. Therefore, host suppressor cells may play a part in the decreased capacity of B lymphocytes to secret immunoglobulin in certain patients with myeloma.

Adolescent↗