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.

Martincic K, S Alkan, A Cheatle, L Borghesi & C Milcarek
Transcription elongation factor ELL2 directs Ig secretion in plasma cells by stimulating altered RNA processing.
Nat Immunol (2009) 10:1102-1109
Pal R, M Janz, D Galson, M Gries, S Li, K Johrens, I Anagnostopoulos, et al.
C/EBP{beta} regulates transcription factors critical for proliferation and survival of multiple myeloma cells.
Blood (2009) 114:3890-3898
Vallejo A, J Michel, L Bale, B Lemster, L Borghesi & C Conover
Resistance to age-dependent thymic atrophy in long-lived mice that are deficient in PAPPA.
PNAS (2009) 106:11252-11257
Esplin B, R Welner, Q Zhang, L Borghesi & P Kincade
A differentiation pathway for B1 cells in adult bone marrow.
PNAS (2009) 106:5773-5778
Borghesi L
Obama must match science rhetoric with action.
Nature (2009) 457:26
Yang Q, L Kardava, A St Leger, K Martincic, B Varnum-Finney, I Bernstein, C Milcarek & L Borghesi
E47 controls the developmental integrity and cell cycle quiescence of multipotential hematopoietic progenitors.
J Immunol (2008) 181:5885-5894
Pilbeam K, P Basse, L Brossay, N Vujanovic, R Gerstein, A Vallejo & L Borghesi
The ontogeny and fate of natural killer cells marked by permanent DNA rearrangements.
J Immunol (2008) 180:1432-1441
Welner R, R Pelayo, Y Nagai, K Garrett, T Wuest, D Carr, L Borghesi, M Farrar & P Kincade
Lymphoid precursors are directed to produce dendritic cells as a result of TLR9 ligation during herpes infection.
Blood (2008) 9:3753-3761
Borghesi L & C Milcarek
Innate versus adaptive immunity: A paradigm past its prime?
Cancer Res (2007) 67:3989-3993
Borghesi L, J Aites, S Nelson, P Lefterov, P James & R Gerstein
E47 is required for V(D)J recombinase activity in common lymphoid progenitors.
J Exp Med
(2005) 12:1669-1677
Borghesi L, L-Y Hsu, J Miller, M Anderson, L Herzenberg, L Herzenberg, M Schlissel, D Allman & R Gerstein
B lineage-specific regulation of V(D)J recombinase activity is established in common lymphoid progenitors.
J Exp Med (2004) 199: 491-502
Borghesi L & R Gerstein
Developmental separation of V(D)J recombinase expression and initiation of IgH recombination in B lineage progenitors.
J Exp Med (2004) 199: 483-489