Studies on β2-microglobulin. II. On its Production in Human Lymphocytes and Human Cancer Cells

Production of β2-microglobulin (β2μ) by peripheral lymphocytes obtained from 25 normal controls and patients with various diseases, and 7 established lines of human cancer cells was investigated in an in vitro culture system. Concentrations of β2μ were determined by radioimmunoassay, and the presence of β2μ in these cells was demonstrated by immunofluorescent technique. The results obtained were as follows. 1) Production of β2μ by lymphocytes was significantly increased after stimulation with PHA in contrast to that determined in the unstimulated culture, and a comparison was run against that after stimulation with Pokeweed mitogen. 2) Concentrations of PHA in a range of 1 to 20μ?/million cells were constantly stimulatory, and the increase of production after PHA stimulation showed its peak response on the 3rd or 4th day. The time course studies of production suggested that β2μ might be related with the basic intracellular protein metabolism rather than the cell proliferation. 3) Production of β2μ by lymphocytes was poorly correlated with the number of E-rosette forming cells in cultured lymphocytes, but it showed a significant correlation with the percentage of blastoid cells emerging in the mitogen stimulated culture. 4) Production of β2μ by peripheral lymphocytes of a patient with B cell CLL was remarkably depressed, however, in a case of B cell CLL with normal number of E-rosette forming cells in remission did not show a reduction of the production. The β2μ production by lymphocytes in the case of T cell CLL was higher than that in B cell CLL, and the results suggested that β2μ was elaborated to a considerable extent by thymus-dependent lymphocytes. 5) Production of β2μ by cancer cells demonstrated in the established cell lines was changeable from line to line, showing relatively higher production at a cell level compared to that of lymphocyte, and it was suggested that the relatively higher levels of serum β2μ found in cancer patients may be related with these findings. 6) Chromatographic studies on Sephadex G-100 suggested the possibility that a part of β2μ secreted from cultured lymphocytes might be associated with HL-A antigens, and a discussion was made on the possible correlation of β2μ with HL-A antigens