Effect of a bcl-2 transgene on production and localization of precursor B cells in mouse bone marrow
- Author(s)
- Janani, R; Harris, AW; Strasser, A; Dhanoa, S; Plyam, R; Osmond, DG;
- Details
- Publication Year 1998-09,Volume 26,Issue #10,Page 982-990
- Journal Title
- EXPERIMENTAL HEMATOLOGY
- Publication Type
- Journal Article
- Abstract
- 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 mit otic arrest were used to quantitate the number and proliferative activity of u(-) pro-B cells (terminal deoxynucleotidyl transferase [TdT](+)B220(-), TdT(+)220(+), and TdT(-)B220(+)); pre-B cells (c mu(+)); and B cells (s mu(+)). 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 I-125-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 IgD(high) mature B lymphocytes. In contrast, many other IgM(+) and IgD(low) 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.
- Publisher
- CARDEN JENNINGS PUBL CO LTD
- Keywords
- ANTI-IGM ANTIBODY; LYMPHOCYTE-B; CAENORHABDITIS-ELEGANS; ENDOPLASMIC-RETICULUM; INVIVO PERFUSION; NUCLEAR-ENVELOPE; CLONAL DELETION; BEARING CELLS; SCID MICE; DEATH
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Creation Date: 1998-09-01 12:00:00