The authors generated transgenic mice (termed Cd19-cre Pax5fl/− mice) in which the Pax5 gene is conditionally switched off in mature B cells that express the B-cell marker CD19. Within 8 months, half of the mice had died after developing aggressive lymphoma. The tumour cells expressed some markers typical of progenitor cells but were also found to contain rearranged immunoglobulin genes leading the authors to conclude that the lymphomas arose from mature B cells and not from progenitor cells. This suggested that some dedifferentiation of B cells had occurred.
To address the plasticity of mature B cells in the absence of oncogenic events, the authors developed techniques to isolate highly purified Pax5-deleted mature B cells, with the deletion events occurring either in vivo or in vitro. Isolated mature Pax5-deleted B cells were transplanted into mice deficient for the recombination-activating gene 2 (Rag2), which cannot generate mature B or T cells. Recipient mice showed robust reconstitution of T-cell development, consistent with the dedifferentiation of Pax5-deleted mature B cells into progenitor cells in the bone marrow; these cells could then seed the thymus and subsequently develop into T cells. Within 2–3 months, the mice had a typical distribution of double negative (CD4−CD8−), double-positive (CD4+CD8+), and single positive (CD4+ or CD8+) thymocytes. In contrast to wild-type T cells, these T cells also carried rearrangements of distinct immunoglobulin gene families.
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