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. The E protein family of transcription factors - and notably the E family member E47 - is critical for progression of bone marrow stem cells to the lymphoid lineages but the precise mechanisms remain unknown. One of our goals is to understand the molecular targets of E47 transcriptional activity, and how this factor directs progenitors to the B lymphoid lineage while restraining other lineage fate options.

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, diabetes and lupus. 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.

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