Cross section through bone marrow - negative control
A cross section through a femur from a control, non-transgenic mouse. Compare this background fluorescence to the green fluorescence expressed by B lineage progenitors expressing rag2-GFP in slide 4.
B cell development in situ
A cross section through a murine femur reveals B lineage progenitors nestled within the bone cavity.
Lymphocytes within the bone marrow (upper right) are outlined in faint green; greenish line at lower left is edge of bone.
Tracing rag2-GFP expression in T cells
Green fluorescence marks T cell progenitors undergoing V(D)J recombination to assemble a T cell receptor. Slide 6 shows this same section under transmitted light. Note that virtually all T cells express rag2.
Compare to rag2 expression in bone marrow B cells, slide 4.
Tracing rag2-GFP expression in B cells
Dim green fluorescence marks B lineage progenitors (middle and upper right) undergoing V(D)J recombination to make antibodies. Slide 2 show this B cell section under transmitted light, and slide 1 shows a comparable image from a control mouse that does not express rag2-GFP.
Note that rag2+ B lymphocytes in bone marrow are rare as compared to rag2+ T cells in the thymus (slide 3). This is because B cell precursors are not the only hematopoietic subset in the bone marrow while T cell precursors form the bulk of thymus cells.
developing B lymphocytes
B lineage progenitors (small, round) receive critical developmental signals from bone marrow stromal cells (larger, adherent).
thymus cross section
The thymus is packed full of developing T lineage progenitors. Visualize which cells are in the process of making a T cell receptor by seeing this same section with fluorescent imaging in slide 3.
New & Notable...
Rashmi wins Alec G. Stewart Student Achievement Award
Patti invited to give oral talk at 2013 AAI (Honolulu!);
merits travel award for same.
Lisa awarded $400K NIH SIG grant.
Hematopoietic stem cells can be injured. The Borghesi lab studies the pathways that maintain stem cell quality. Multipotent stem cells are the source of all white blood cells of the immune system. Infection, radiation exposure, chronic autoimmunity and even chronologic aging can diminish stem cell function. Indeed, the elderly amongst us are one of the hardest groups to vaccinate effectively due, in part, to diminished lymphocyte production. We are working to determine if stem cell injury can be reversed.
Our work over the last decade defines a major role for the E47 transcription factor in regulating hematopoietic stem cell function as well as downstream B lymphocyte production and antibody formation. In the absence of E47, stem cells proliferate to exhaustion and fail to produce antibody-secreting B lymphocytes. Moreover, we have linked E47 overexpression to the B cell cancer CLL. Our findings provide a molecular mechanism for the stem cell exhaustion that frequently accompanies diseases of chronic inflammation, and suggests new opportunities for therapy.
To get more details about our lab projects, lab
people, and the fun research environment at Pitt, follow this link.
also, visit our Pitt Flow Cytometry website &
Lisa's profile as one-half of a Dual Academic Couple