Flt3 ligand plus IL-7 supports the expansion of murine thymic B cell progenitors that can mature intrathymically.
Flt3 ligand (flt3L) has potent effects on hemopoietic progenitors, dendritic cells, and B lymphopoiesis. We have investigated the effects of flt3L on intrathymic precursors. The addition of flt3L + IL-7 to lobe submersion cultures of murine fetal thymic lobes resulted in the expansion of an immature population of Thy-1(low), CD44(high), HSA(high) cells. This population contained cells with precursor activity, as determined by their capacity to repopulate deoxyguanosine-treated fetal thymic lobes. Upon reentry to the thymic lobe, flt3L + IL-7-cultured Thy-1(low), CD44(high), HSA(high) cells underwent expansion and differentiation into B cells. Two weeks after fetal thymic organ culture following thymic lobe reconstitution, intrathymic cells were Thy-1-, B220+, and a subset was sIgM+. The intrathymic B cells shared features of adult thymic B cells, including CD5 expression and proliferative responses to IL-4 + IL-5 + CD40 ligand, but not to LPS or soluble anti-IgM. Ig production was noted upon stimulation with IL-4 + IL-5 + LPS and IL-4 + IL-5 + CD40 ligand. In conclusion, we have demonstrated that flt3L + IL-7 supports the expansion of a subset of progenitors present in the fetal thymus. The cultured progenitors can repopulate a fetal thymic lobe and develop into mature functional B cells, demonstrating that the fetal thymus is able to support B cell as well as T cell development.
McKenna
H J
HJ
Department of Immunobiology, Immunex Corporation, Seattle, WA 98101, USA. mckenna@immunex.com
Morrissey
P J
PJ
D000818:Animals; D001402:B-Lymphocytes / Q000502:physiology*; D006410:Hematopoiesis / Q000187:drug effects*; D006412:Hematopoietic Stem Cells / Q000502:physiology*; D007136:Immunoglobulins / Q000096:biosynthesis; D015851:Interleukin-7 / Q000494:pharmacology*; D008213:Lymphocyte Activation; D008565:Membrane Proteins / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D013950:Thymus Gland / Q000166:cytology*
D007136:Immunoglobulins; D015851:Interleukin-7; D008565:Membrane Proteins; C084881:flt3 ligand protein