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Mechanism of the Growth-Promoting Effect of Serum Albumin on Concanavalin A-Activated Lymphocytes: Protective Effect of the Plasma Proteins¹

Department of Pathology, Peter Bent Brigham Hospital and Harvard Medical School, Boston, Massachusetts 02115

Abstract

The concentration of concanavalin A (Con A) required for optimal growth of lymphocytes is 10 to 20 times greater in the presence of plasma than in the presence of serum albumin (BSA). This shift in Con A requirement is mainly caused by Cohn fractions III and IV, which bind and probably remove free Con A. Lymphocytes, once they are activated by Con A, lose all proliferative activity unless protected by certain proteins. Cohn fraction VI and -lactoglobulin were found to be most effective in protecting the cells. The protective proteins do not promote growth; only BSA promotes growth of Con A-activated lymphocytes. The mechanism of the growth-promoting effect of BSA of Con A-activated lymphocytes was investigated. The continuous presence of BSA in the culture medium during and after Con A activation is required for optimal lymphocyte growth. Temporary replacement of BSA by any of the protective proteins markedly reduces, whereas protein-free medium abolishes, growth. The mechanism of the growth-promoting effect of BSA is not concerned with regulating the uptake of Con A by lymphocytes. Red blood cells, crenated by washing in protein-free medium, revert immediately to their normal globular shape by the addition of BSA or FAF BSA, whereas the protective proteins fail to do so, indicating a direct effect of BSA on the external surface of the erythrocyte membrane and presumably also of the lymphocyte. The hypothesis is proposed that BSA promotes growth by conveying total structural integrity to the cell surface membrane of Con A-treated lymphocytes.

Footnotes

¹ This work was supported by Grants HL-06370 and AM-17158 from the National Institutes of Health, United States Public Health Service.

² Helga Spieker-Polet is supported by Training Grant HL-7066.