The BCL2 protein is topographically restricted in tissues characterized by apoptotic cell death. The BCL2 protooncogene encodes an inner mitochondrial membrane protein that blocks programmed cell death. BCL2 was isolated from the chromosomal breakpoint of follicular B-cell lymphoma. Transgenic mice that overexpress BCL2 display extended survival of resting B cells. In this study, the distribution of BCL2 protein within organized tissues was defined using a monospecific anti-human BCL2 antibody. BCL2 is restricted within germinal centers to the follicular mantle and to portions of the light zone implicated in the selection and maintenance of plasma cells and memory B cells. BCL2 is present in the surviving T cells in the thymic medulla. All hematopoietic lineages that derive from a renewing stem cell also display BCL2. A limited number of nonlymphoid tissues demonstrate BCL2 and can be grouped as (i) glandular epithelium in which hormones or growth factors regulate hyperplasia and involution, (ii) complex differentiating epithelium such as skin and intestine characterized by long-lived stem cells, and (iii) long-lived postmitotic cells such as neurons. Within these tissues that demonstrate apoptotic cell turnover, BCL2 is often topographically restricted to long-lived or proliferating cell zones. BCL2's function as an antidote to apoptosis may confer longevity to progenitor and effector cells in these tissues. BCL2 is unique among protooncogenes by being localized to the inner mitochondrial membrane. Moreover, BCL2 has the oncogenic function of blocking programmed cell death. Deregulated BCL2 extends the survival of certain hematopoietic cell lines following growth factor deprivation. When pro-B-cell or promyelocyte cell lines are deprived of interleukin 3 they normally succumb to a programmed demise entitled apoptosis. This pattern of morphologic cell death is characterized by a dramatic plasma membrane blebbing, cell volume contraction, nuclear pyknosis, and internucleosomal DNA degradation following the activation of a Ca²+/Mg²⁺-dependent endonuclease. Overexpression of mitochondrial BCL2 is an antidote to this process. BCL2 extends the survival of such cells independent of affecting their proliferation. The BCL2 protooncogene was discovered at the chromosomal breakpoint of the t(14;18) found in human follicular lymphoma. The t(14;18) juxtaposes the BCL2 gene from chromosome 18 with the immunoglobulin heavy chain (IGH) locus on 14. This creates a BCL2-IGH fusion gene that is markedly deregulated, resulting in overproduction of BCL2 RNA and protein. BCL2-IG transgenic mice overexpress BCL2 in lymphoid tissues and develop a polyclonal expansion of smallThe BCL2 protein is topographically restricted in tissues characterized by apoptotic cell death. The BCL2 protooncogene encodes an inner mitochondrial membrane protein that blocks programmed cell death. BCL2 was isolated from the chromosomal breakpoint of follicular B-cell lymphoma. Transgenic mice that overexpress BCL2 display extended survival of resting B cells. In this study, the distribution of BCL2 protein within organized tissues was defined using a monospecific anti-human BCL2 antibody. BCL2 is restricted within germinal centers to the follicular mantle and to portions of the light zone implicated in the selection and maintenance of plasma cells and memory B cells. BCL2 is present in the surviving T cells in the thymic medulla. All hematopoietic lineages that derive from a renewing stem cell also display BCL2. A limited number of nonlymphoid tissues demonstrate BCL2 and can be grouped as (i) glandular epithelium in which hormones or growth factors regulate hyperplasia and involution, (ii) complex differentiating epithelium such as skin and intestine characterized by long-lived stem cells, and (iii) long-lived postmitotic cells such as neurons. Within these tissues that demonstrate apoptotic cell turnover, BCL2 is often topographically restricted to long-lived or proliferating cell zones. BCL2's function as an antidote to apoptosis may confer longevity to progenitor and effector cells in these tissues. BCL2 is unique among protooncogenes by being localized to the inner mitochondrial membrane. Moreover, BCL2 has the oncogenic function of blocking programmed cell death. Deregulated BCL2 extends the survival of certain hematopoietic cell lines following growth factor deprivation. When pro-B-cell or promyelocyte cell lines are deprived of interleukin 3 they normally succumb to a programmed demise entitled apoptosis. This pattern of morphologic cell death is characterized by a dramatic plasma membrane blebbing, cell volume contraction, nuclear pyknosis, and internucleosomal DNA degradation following the activation of a Ca²+/Mg²⁺-dependent endonuclease. Overexpression of mitochondrial BCL2 is an antidote to this process. BCL2 extends the survival of such cells independent of affecting their proliferation. The BCL2 protooncogene was discovered at the chromosomal breakpoint of the t(14;18) found in human follicular lymphoma. The t(14;18) juxtaposes the BCL2 gene from chromosome 18 with the immunoglobulin heavy chain (IGH) locus on 14. This creates a BCL2-IGH fusion gene that is markedly deregulated, resulting in overproduction of BCL2 RNA and protein. BCL2-IG transgenic mice overexpress BCL2 in lymphoid tissues and develop a polyclonal expansion of small