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Published on: November 8, 2011
Proliferative response of B chronic lymphocytic leukemia lymphocytes stimulated with IL2 and soluble CD23
A Brizard1, F Morel, J C Lecron
1Département d'Hématologie et Oncologie Médicale, (CNRS URA 1172), CHU La Milétrie, Poitiers, France.
Insights
Soluble CD23 (sCD23) enhances Interleukin-2 (IL2)-induced proliferation in B-chronic lymphocytic leukemia (B-CLL) cells, suggesting a protective role against apoptosis. High sCD23 levels in patients may indicate an autocrine or paracrine activation loop.
Area of Science:
- Immunology
- Hematology
- Cell Biology
Background:
- B-chronic lymphocytic leukemia (B-CLL) is a heterogeneous lymphoproliferative disorder.
- The role of CD23, a B-cell growth factor receptor, in B-CLL pathogenesis is not fully understood.
- Soluble CD23 (sCD23) levels are elevated in B-CLL patients.
Purpose of the Study:
- To investigate the in vitro proliferative effects of sCD23 on B-CLL lymphocytes.
- To compare the response to sCD23 with other known B-cell mitogens and cytokines.
- To explore the potential role of sCD23 in B-CLL cell survival and activation.
Main Methods:
- Purified B-CLL lymphocytes were cultured with various stimuli including sCD23, IL2, PMA, SAC, IL1, IL4, IL6, and interferons.
- Proliferative responses were measured.
- CD23 membrane expression and sCD23 levels in culture supernatants were assessed.
Main Results:
- B-CLL cells proliferated in response to PMA, SAC, and IL2, with IL2 response enhanced by IFN-alpha or IFN-gamma.
- sCD23 alone, or with IL1, IL4, or IL6, did not induce proliferation.
- sCD23 significantly increased IL2-induced proliferation, suggesting an anti-apoptotic effect.
- High serum sCD23 and membrane CD23 expression were observed in patients.
- CD23 expression was lost in culture except with PMA stimulation; high sCD23 was found in PMA-stimulated supernatants.
Conclusions:
- sCD23 may play a role in B-CLL cell survival by enhancing IL2-mediated proliferation.
- Elevated sCD23 in B-CLL patients suggests a potential autocrine or paracrine activation loop.
- Further research is warranted to elucidate the precise mechanisms of sCD23 involvement in B-CLL.
Abstract:
The in vitro proliferative response of purified B-chronic lymphocytic leukemia (B-CLL) lymphocytes cultured in the presence of soluble CD23 (sCD23) with or without IL2 was compared to the responses induced by phorbol 12-myristate 13-acetate (PMA), Staphylococcus aureus strain Cowan I (SAC), IL1, IL2, IL4, IL6 and the combination of IL2 and interferon (IFN) alpha or IFN gamma. As expected, B-CLL lymphocytes proliferated with PMA, SAC and IL2 with a clear enhancement of the IL2-induced response by IFN alpha or IFN gamma. They failed to proliferate in response to sCD23, IL1, IL4 or IL6 alone nor to the combinations of sCD23 and any of the 3 latter cytokines. However, sCD23 significantly increased the proliferation of B-CLL cells induced by IL2, suggesting a protective effect of sCD23 on apoptosis. Serum levels of sCD23 and CD23 membrane expression were high in every patient which is compatible with the hypothesis of an autocrine or paracrine activation loop. Detectable CD23 expression was lost in all cultures except for that stimulated by PMA. Only supernatants of PMA-stimulated cultures contained high sCD23 levels.

