Effect of a bcl-2 transgene on production and localization of precursor B cells in mouse bone marrow.
Many B cell precursors die while differentiating in mouse bone marrow. To ascertain the mechanisms involved in this process, populations of B lineage cells and their tissue localization were analyzed in bone marrow of transgenic mice overexpressing the apoptosis inhibitor, Bcl-2. Immunofluorescence labeling and mitotic arrest were used to quantitate the number and proliferative activity of mu- pro-B cells (terminal deoxynucleotidyl transferase [TdT]+B220-, TdT+B220+, and TdT-B220+); pre-B cells (cmu+); and B cells (smu+). Mature B cells (IgM+IgD+) were increased 16- to 20-fold. In addition, immature B lymphocytes (IgM+IgD-/low), representing newly formed cells, were increased three- to sixfold, whereas pre-B cells and late pro-B cells were increased 30 to 60% in production rate. Earlier pro-B cells expressing TdT were unaffected. In spleen, both mature and immature B cells were greatly increased, but cells of precursor phenotype were few and TdT+ cells were absent. The in vivo location of B cells was examined by autoradiography using light and electron microscopy after intravenous injection of 125I-labeled antibodies. B lineage cells (B220+) were increased throughout bone marrow, often within dilated venous sinusoids, particularly in subosteal regions. Many intravascular and perisinusoidal cells were IgDhigh mature B lymphocytes. In contrast, many other IgM+ and IgDlow immature B lymphocytes clustered extravascularly around the central venous sinus. Plasma cells with distended endoplasmic reticulum were numerous. These findings provide evidence that, in addition to expanding the recirculating pool of B cells entering bone marrow from the blood stream, high levels of Bcl-2 can inhibit some of the apoptosis occurring during B cell differentiation, thereby expanding populations of B lymphopoietic precursor cells within the bone marrow parenchyma.
Janani
R
R
Department of Anatomy and Cell Biology, McGill University, Montreal, Quebec, Canada.
Harris
A W
AW
Strasser
A
A
Dhanoa
S
S
Plyam
R
R
Osmond
D G
DG
D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D001402:B-Lymphocytes / Q000276:immunology*; D001853:Bone Marrow / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology; D019070:Cell Lineage; D019254:Genes, bcl-2; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D013234:Stem Cells / Q000276:immunology