In vitro beta2-microglobulin (β2m) secretion by normal and leukaemic B-cells: effects of recombinant cytokines and evidence for a differential response to the combined stimulus of phorbol ester and calcium ionophore

GM‐CSF RAISES SERUM LEVELS OF β2‐MICROGLOBULIN AND THYMIDINE KINASE IN PATIENTS WITH CHRONIC LYMPHOCYTIC LEUKAEMIA

“…In a recent abstract of the analysis of 622 patients, serum b 2 m was found to be the most powerful prognostic factor in CLL; b 2 m was more strongly associated with response and survival than Rai or Binet stage (Keating et al, 1995). Serum b 2 m production rates may also correspond to the degree of B-cell differentiation, and/or to the degree of cellular activation ( Jones et al, 1990). Serum b 2 m rose initially in all our patients treated with GM-CSF and in three patients the value fell back to the baseline during GM-CSF treatment; in five patients serum b 2 m remained elevated.…”

“…Alternatively, GM-CSF may enhance the expression of class I HLA antigens directly or indirectly, possibly via activation of the cytokine network. In vitro, the recombinant cytokines IL-1, IL-2, interferon-alpha, interferon-gamma and tumour necrosis factor have been observed to enhance the production of b 2 m of both normal and leukaemic B cells ( Jones et al, 1990). In multiple myeloma and chronic myeloproliferative diseases, administration of interferon-alpha at clinical doses has been shown to cause a rapid increase in serum b 2 m concentration (Remes et al, 1993).…”

Synthesis and Turnover of β2-Microglobulin in Ad12-transformed Cells Defective in Assembly and Transport of Class I Major Histocompatibility Complex Molecules

“…Based on our previous immunoprecipitation data and on other studies (45)(46)(47)(48)(49), it seemed likely that in normal cells most of the ␤ 2 m molecules would be associated with class I heavy chains and free molecules would either be degraded or secreted. Several studies have shown that free ␤ 2 m is secreted from cells and that its secretion can be enhanced by various cytokines, growth factors, and growth promoters (47)(48)(49). Dragmont et al (45) demonstrated that free ␤ 2 m was secreted into the culture media of cell lines independent of cell surface expression of class I heavy chains.…”

“…Dragmont et al (45) demonstrated that free ␤ 2 m was secreted into the culture media of cell lines independent of cell surface expression of class I heavy chains. ␤ 2 m has also been shown to be secreted from endometrial cells (46), leukemic B cells (47), fibroblasts (48), and hepatocytes (49). Much less is known about the degradation pathway of free ␤ 2 m within the cells.…”