Abstract
B lymphopoiesis in bone marrow (BM) is critical for maintaining a diverse peripheral B cell pool to fight infection and establish lifelong immunity. The generation of immature B cells is reduced in Flt3-ligand (FL-/-) mice leading to deficiencies in splenic B cells. Here, we sought to understand the cellular basis of the spleen B cell deficiency in FL-/-mice. Significant reductions in transitional (TS) and follicular (FO) B cells were found in FL-/-mice, and increased frequencies, but not absolute numbers, of marginal zone (MZ) B cells. BAFF-R expression on splenic B cells and serum levels of B cell activating factor (BAFF) was comparable to wildtype (WT) mice. Mixed BM chimeras revealed that the reductions in TS and FO B cells were cell extrinsic. FL administration into FL-/-mice restored the deficiency in TS B cells and normalized the MZ compartment. Ki67 analysis revealed a significant decrease in the proliferative capacity of TS B cells in FL-/-mice. A Bcl2 transgene did not rescue TS cells in FL-/-mice, uncoupling FL-deficiency to Bcl2-dependent survival pathways. Upregulation of CD1d expression and adoptive transfer experiments suggested MZ skewing in FL-/-mice. These findings support an integral role for Flt3 signaling in peripheral B cell maturation.
Original language | English (US) |
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Pages (from-to) | 103-117 |
Number of pages | 15 |
Journal | Immunity, inflammation and disease |
Volume | 3 |
Issue number | 2 |
DOIs | |
State | Published - Jun 2015 |
Externally published | Yes |
Keywords
- B cell maturation
- B lymphopoiesis
- BAFF
- Flt3 signaling
- Follicular B cells
- Marginal zone B cells
- Proliferation
- Transitional B cells
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology