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Interleukin-7 partially rescues B-lymphopoiesis in osteopetrotic oc/oc mice through the engagement of B220+ CD11b+ progenitors.

Abstract : OBJECTIVE: We recently identified in the mouse bone marrow a B-lymphoid/myeloid B220+ CD11b+ progenitor population. This population is accumulated in the osteopetrotic oc/oc mouse, which suggests that it could be controlled by bone marrow factors whose expression varies in this pathologic bone environment. Among the possible factors, interleukin (IL)-7 is involved in the control of B lymphopoiesis and osteoclastogenesis. Therefore, we hypothesized that IL-7 could regulate the accumulation of the B220+ CD11b+ population in oc/oc mice. METHODS: B220+ CD11b+ cells sorted from oc/oc mice were treated with IL-7 and their phenotype was analyzed by flow cytometry and real-time reverse transcriptase polymerase chain reaction (RT-PCR). In vivo, IL-7 was injected in oc/oc mice, and B220+ CD11b+ and B cells, as well as B-cell proliferation and apoptosis, were analyzed by flow cytometry. The expression of B lymphopoiesis and myelopoiesis markers was analyzed by real-time RT-PCR. RESULTS: In vitro, IL-7 induced the differentiation of B220+ CD11b+ cells into B lymphocytes through the induction of Pax5 and the inhibition of myeloid markers. In vivo, IL-7 injections in oc/oc mice induced a decrease of the B220+ CD11b+ population and the partial restoration of B-cell population, which was reduced in oc/oc mice. In parallel, upon IL-7 injections, Pax5 expression was induced in B220+ cells and B-cell apoptosis was reduced. CONCLUSIONS: Our results demonstrate that IL-7 injection can partially rescue B lymphopoiesis in oc/oc mice through the engagement of the B220+ CD11b+ population in the B-lymphoid pathway. Therefore, IL-7 delivery could represent a new therapeutic perspective to circumvent the lymphopenia observed in infantile malignant osteopetrosis patients.
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https://www.hal.inserm.fr/inserm-00104152
Contributor : Georges Carle <>
Submitted on : Thursday, October 5, 2006 - 6:51:41 PM
Last modification on : Monday, October 12, 2020 - 10:27:44 AM

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Claudine Blin-Wakkach, Abdelilah Wakkach, Danielle Quincey, Georges F Carle. Interleukin-7 partially rescues B-lymphopoiesis in osteopetrotic oc/oc mice through the engagement of B220+ CD11b+ progenitors.. Experimental Hematology, Elsevier, 2006, 34 (7), pp.851-9. ⟨10.1016/j.exphem.2006.04.003⟩. ⟨inserm-00104152⟩

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