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Effect of recombinant human interleukin 2 (rIL-2) on normal peripheral blood B cells and B lymphoblastoid cell lines
Insights
Interleukin 2 (IL-2) promotes normal B cell growth but inhibits malignant B cells in non-Hodgkin
Area of Science:
- Immunology
- Hematology
- Oncology
Background:
- The role of interleukin 2 (IL-2) in B cell malignancies is not fully understood.
- Normal and malignant B cells exhibit varying responses to IL-2.
- The IL-2 receptor (IL-2R) alpha chain (CD25) is expressed on some B non-Hodgkin's lymphoma (NHL) cells.
Purpose of the Study:
- To investigate the functional responsiveness of normal peripheral blood B cells and B cell lines from patients with NHL to recombinant human IL-2 (rIL-2).
- To determine if rIL-2 affects the proliferation, differentiation, and clonal growth of malignant B cells.
Main Methods:
- Assessed normal peripheral blood B cells and NHL cell lines for responsiveness to rIL-2.
- Utilized [3H]thymidine uptake assays to measure proliferation.
- Employed clonogenic culture assays to evaluate colony formation.
- Measured Ig production to assess differentiation.
Main Results:
- Normal peripheral blood B cells showed a dose-dependent proliferative response to rIL-2.
- NHL cell lines did not proliferate in response to rIL-2.
- rIL-2 moderately inhibited the clonal growth of NHL cells by 28-41% without inducing differentiation.
- NHL cell lines expressed CD25 (IL-2R alpha chain) at varying percentages (28-57%).
Conclusions:
- Malignant B cells in NHL can express the IL-2 receptor (CD25).
- Despite CD25 expression, NHL cells exhibit functional unresponsiveness to IL-2-driven proliferation.
- rIL-2 demonstrates an inhibitory effect on the clonal growth of malignant B cells, suggesting a potential therapeutic avenue.
Abstract:
The role of interleukin 2 (IL-2) for growth and differentiation of normal and malignant B cells still remains controversial. We assessed normal peripheral blood B cells and cell lines derived from patients with B non-Hodgkin's lymphomas (NHLs) with respect to their responsiveness to recombinant human IL-2 (rIL-2). The NHL cell lines used in our experiments expressed the Tac antigen (CD25)--a compound of the IL-2 receptor (IL-2R)--in a percentage ranging from 28 to 57%. As measured in a [3H]thymidine uptake assay, the normal peripheral blood B cells demonstrated a dose-dependent proliferative response to rIL-2, whereas the NHL cells did not show any responsiveness to rIL-2. In a clonogenic culture assay we evaluated the colony formation of the NHL cells and found a decrease of 28 to 41% on average in the presence of rIL-2 (10-50 U/ml). This moderate inhibitory effect on the clonal growth of the NHL cells was not due to a differentiation inducing effect of rIL-2, as studied by measuring the Ig production under increasing doses of rIL-2 (1 to 100 U/ml). Thus, malignant NHL B cells may express the CD25 compound of the IL-2 receptor on their surface, demonstrating a different functional responsiveness to rIL-2 compared to normal peripheral blood B cells.
