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.

The Borghesi lab studies immune system development with a specific focus on B cells. B lymphocytes are the cells of the immune system that produce antibodies. Some of the transcription factors that control normal B cell development are also implicated in B cell leukemias, and we are beginningto dissect the regulatory pathways that have gone awry in these cancer cells.

Patients lacking B cells because of a congenital defect or disease therapy are at risk of major infection. Conversely, misguided B cell activity can contribute to autoimmune disorders such as rheumatoid arthritis. We are working to understand the molecular pathway that regulates B cell development and antibody production with the goal of identifying targets for disease therapy.

B cells are not the only thing we do! To get more details about our lab projects, lab people, and the unique research environment at Pitt, follow this link.

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