B cell production and turnover in CBA/Ca, CBA/N and CBA/N-bcl-2 transgenic mice: xid-mediated failure among pre B cells is unaltered by bcl-2 overexpression.
The CBA/N strain carries xid, a murine btk missense mutation that reduces peripheral B cell numbers. Using in vivo BrdU labeling and cytofluorimetry, we have compared the magnitude, production rates, and turnover rates of each B lineage subset in the marrow and periphery of CBA/Ca and CBA/N mice. Our results show the pro-B compartment is largely unaffected by xid. In contrast, the pre-B cell pool is markedly reduced, reflecting a diminished production rate and unaltered turnover time. Despite diminished pre-B cell formation, the size of the immature B cell pool is relatively normal in CBA/N mice, due to increased proportional survival of pre-B cells. In addition, we have assessed the marrow and peripheral B cell subsets of CBA/N mice transgenic for bcl-2. These results indicate that while the bcl-2 transgene promotes lengthened survival in most B cell subsets, the pro/pre-B cell losses mediated by xid are not abrogated by bcl-2 overexpression. Taken together, these findings suggest that the initial [not readable: see text] from the pro- to pre-B cell pools, and that anomalies in subsequent compartments likely reflects the action of homeostatic mechanisms compensating for compromised pre-B cell production.
Cancro
M P
MP
Univ. of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
Sah
A P
AP
Levy
S L
SL
Allman
D M
DM
Constantinescu
D
D
Schmidt
M R
MR
Woodland
R T
RT
D000077329:Agammaglobulinaemia Tyrosine Kinase; D000818:Animals; D016175:B-Lymphocyte Subsets / Q000276:immunology / Q000473:pathology*; D001853:Bone Marrow / Q000473:pathology; D016923:Cell Death; D002454:Cell Differentiation; D002470:Cell Survival; D005260:Female; D018507:Gene Expression Regulation, Developmental; D019254:Genes, bcl-2; D006410:Hematopoiesis / Q000235:genetics; D006412:Hematopoietic Stem Cells / Q000276:immunology / Q000473:pathology*; D006706:Homeostasis; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000201:enzymology / Q000235:genetics / Q000276:immunology / Q000473:pathology*; D008213:Lymphocyte Activation; D018655:Lymphocyte Count; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D008822:Mice, Transgenic; D020125:Mutation, Missense; D011505:Protein-Tyrosine Kinases / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000502:physiology*; D013154:Spleen / Q000473:pathology
D019253:Proto-Oncogene Proteins c-bcl-2; D011505:Protein-Tyrosine Kinases; D000077329:Agammaglobulinaemia Tyrosine Kinase; C000625949:BTK protein, human; C000625951:Btk protein, mouse