Abstract
Little is known about the effects of ionizing radiation on the transition and the related signal transduction of progenitor B cells in the bone marrow. Thus, using an NIH Swiss mouse model, we explored the impact of ionizing radiation on the early stage of B-cell development via an examination of the transition of CLP to pro-B to pre-B cells within bone marrow as a function of radiation doses and times. Our results showed that while the total number of bone marrow lymphoid cells at different stages were greatly reduced by subtotal body irradiation (sub-TBI), the surviving cells continued to transition from common lymphoid progenitors to pro-B and then to pre-B in a reproducible temporal pattern. The rearrangement of the immunoglobulin heavy chain increased significantly 1–2 weeks after irradiation, but no change occurred after 3–4 weeks. The rearrangement of the immunoglobulin light chain decreased significantly 1–2 weeks after sub-TBI but increased dramatically after 3–4 weeks. In addition, several key transcription factors and signaling pathways were involved in B-precursor transitions after sub-TBI. The data indicate that week 2 after irradiation is a critical time for the transition from pro-B cells to pre-B cells, reflecting that the functional processes for different B-cell stages are well preserved even after high-dose irradiation.
Highlights
Bone marrow is the primary tissue that produces hematopoietic stem cells and hosts some transitions from stem cells to differentiated cells, including precursors at different stages in the development of B lymphocytes
The effect of radiation on bone marrow cell count Using the physical parameters of flow cytometry, we studied radiation-induced damage on total bone marrow cells and lymphocytes as a function of doses
The number of total bone marrow cells and lymphocytes in the bone marrow was inversely correlated with the radiation dose (Fig. 1B and 1C)
Summary
Bone marrow is the primary tissue that produces hematopoietic stem cells and hosts some transitions from stem cells to differentiated cells, including precursors at different stages in the development of B lymphocytes. While the stem cells or precursors in bone marrow are extremely vulnerable to radiation, as evidenced by a sharp decline in the number of precursors or stem cells and the number of lymphocytes, neutrophils, and platelets in the peripheral blood [1,2], the bone marrow possesses a powerful repair and regenerative capacity that compensates for the lost cells and maintains homeostasis [3,4]. The protection of immunocompetent cells from radiation damage is essential for their survival. Among these cells, B lymphocytes play a major role in the humoral immune response. B-cell precursors are among the best-characterized hematopoietic precursors, and extensive study of their development has helped to determine potential pathways for the advancement of various blood-cell lineages
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