Karen A. Jacobsen

Upregulation of endogenousp53 and induction of in vivo apoptosis in B-lineage lymphomas ofEμ-myc transgenic mice by deregulated c-myc transgene

Eμ‐myc transgenic mice carry a constitutively overexpressed c‐myc oncogene and develop B‐lineage lymphomas. Previous studies have shown that c‐myc overexpression can lead to in vitro apoptosis. Here, we investigated the in vivo effects of altered c‐myc expression on cell proliferation versus death in spontaneously arising Eμ‐myc tumors. Eμ‐myc tumors display extensive in vivo apoptosis confined to small clusters of cells with greatly increased expression of both the c‐myc transgene and the endogenous p53 gene as compared with that in normal, pretumor, or surrounding tumor tissue. This restricted overexpression of both the c‐myc transgene and the endogenous p53 gene in small clusters of apoptotic tumor cells indicates that overexpression of these genes and apoptosis are not obligatory or uniform during tumor development and suggests that further somatic mutations or microenvironmental influences may be responsible for these properties. Nevertheless, the clear ability of tumor cells to undergo apoptosis in vivo may be exploitable for therapeutic purposes. Mol. Carcinog. 18:66–77, 1997.

Apoptotic Cell Death in the Chicken Bursa of Fabricius

The bursa of Fabricius is the site of primary B cell development in birds, and has been reviewed extensively elsewhere1–3. It is productively colonized during embryonic life by a small number (<50,000) of B lineage committed precursors which undergo immunoglobulin gene rearrangements either prior to their migration to the bursa or within the bursal rudiment during a short window of time in embryonic development. By about day 18 of embryonic development (day e18) all Ig gene rearrangements in the chicken have been completed and the adult B cells compartment is derived from this small pool of rearranged B cell precursors4.

In Vivo Localization of B Lymphoctye Progenitor Cells in Mouse Bone Marrow

The microenvironmental organisation of primary B lymphocytopoiesis in the bone marrow remains poorly understood.

Multiple steps in the regulation and dysregulation of B-cell precursors in the bone marrow: c-myc expression, in vivo effects of interleukins 1 and 7, and stromal cell interactions.

The generation and selection of B lymphocytes in the bone marrow involves a complex series of differentiation steps, molecular interactions with local stromal cells and the influences of both short range and systemic growth factors (Osmond 1986,1990; Kincade 1989,1991). Normal regulation of B lymphopoiesis requires a balance between these various processes. Dysregulations, possibly predisposing to oncogenesis, may result from perturbations at a number of different points in the chain of regulatory events.