CD45-deficient mice accumulate Pro-B cells both in vivo and in vitro.
Efficient generation of mature B lineage cells requires the participation of the BCR, the pre-BCR, accessory coreceptors, and growth factor receptors. Together these receptors integrate cell intrinsic signals with regulatory pathways initiated by surrounding cells and structures. CD45 is a receptor tyrosine phosphatase expressed at high levels on all hemopoietic cells, and has been shown to modulate many signaling cascades in both positive and negative manners. In the absence of B220, the B lineage isoform of CD45, differentiation to the mature B cell stage is incomplete. We demonstrate that CD45-deficient mice also accumulate pro-B cells in the bone marrow. In vitro differentiation is altered in that B lineage populations exhibit prolonged survival in the presence of high concentrations of IL-7. Cell lines derived from CD45-deficient animals experience prolonged JAK/STAT activation in response to IL-7 stimulation, and constitutively elevated levels of phosphorylated src kinases. Aberrant IL-7Ralpha expression is observed in vivo, and may be responsible for the skewed development present in CD45(-/-) animals. Demonstrating that CD45-deficient pro-B cells are affected by the absence of B220 highlights a previously unrecognized parallel in B and T lineage precursors, and emphasizes that the presence of normal numbers of peripheral B cells does not assure that the bone marrow compartment is intact.
Fleming
Heather E
HE
Princess Margaret Hospital, Ontario Cancer Institute, University Health Network, Department of Immunology, University of Toronto, Toronto, Ontario, Canada.
Milne
Craig D
CD
Paige
Christopher J
CJ
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology*; D015153:Blotting, Western; D001853:Bone Marrow / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology*; D002460:Cell Line; D019070:Cell Lineage / Q000276:immunology; D004268:DNA-Binding Proteins / Q000276:immunology / Q000378:metabolism; D004789:Enzyme Activation / Q000276:immunology; D005455:Fluorescent Antibody Technique; D006412:Hematopoietic Stem Cells / Q000276:immunology*; D015851:Interleukin-7 / Q000276:immunology / Q000378:metabolism; D017493:Leukocyte Common Antigens / Q000378:metabolism*; D051379:Mice; D011505:Protein-Tyrosine Kinases / Q000276:immunology / Q000378:metabolism; D011947:Receptors, Antigen, B-Cell / Q000276:immunology / Q000378:metabolism; D020395:Receptors, Interleukin-7 / Q000276:immunology / Q000378:metabolism; D015534:Trans-Activators / Q000276:immunology / Q000378:metabolism
D004268:DNA-Binding Proteins; D015851:Interleukin-7; D011947:Receptors, Antigen, B-Cell; D020395:Receptors, Interleukin-7; D015534:Trans-Activators; D011505:Protein-Tyrosine Kinases; D017493:Leukocyte Common Antigens