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Subpopulations of Human Lymphocytes Defined by ₂-Microglobulin¹

From the Departments of Microbiology and Medicine, Case Western Reserve University and University Hospitals, Cleveland, Ohio 44106

Abstract

A human serum protein with structural homology to immunoglobulins, ₂-microglobulin, was synthesized by normal lymphocytes in vitro. Production of microglobulin was increased when lymphocytes were stimulated with phytohemagglutinin (PHA) or concanavalin A (Con A) but was not increased by stimulation with pokeweed mitogen, suggesting that microglobulin was elaborated by thymus-dependent lymphocytes. Maximal ₂-microglobulin production occurred at a concentration of PHA (2 µg/10⁶ cells) which was far lower than that which led to maximal DNA and protein synthesis. Treatment of normal lymphocytes in culture with anti-₂-microglobulin and complement removed 20% of the cells and abolished ₂-microglobulin production while stimulation of DNA synthesis by PHA was only slightly decreased. Fluorescein coupled antibody to ₂-microglobulin stained virtually all normal lymphocytes, but 15 to 20% stained brightly. Although 15 to 25% of normal lymphocytes stained with anti-light chain antibody, none of these cells stained brightly with antibody to microglobulin when double-staining experiments were performed with two fluorochromes. Lymphocytes from a patient with acquired agammaglobulinemia synthesized microglobulin at a normal rate although the thymus independent (B) cell population as determined by staining for immunoglobulin was less than 3%. On the other hand, synthesis of microglobulin by lymphocytes from four patients with stage IV Hodgkin's disease was minimal. Production of ₂-microglobulin by peripheral lymphocytes of patients with chronic lymphatic leukemia (CLL) was low when the lymphocytes were identified as B-cells; synthesis was normal, however, by lymphocytes lacking surface immunoglobulin in one case of CLL. These results suggest that in man ₂-microglobulin is in large part the product of a thymic dependent lymphocyte subpopulation.

Footnotes

¹ This work was supported by Research Grants AI10148 and AM14700 from the United States Public Health Service.

² Recipient of Career Development Award 5-KO4-AI25732 from the Public Health Service.

³ Scholar of the Leukemia Society of America.