Open AccessCell extrinsic alterations in splenic B cell maturation in Flt3‐ligand knockout mice
Author(s) -
Dolence Joseph J.,
Gwin Kimberly A.,
Shapiro Mariya B.,
Hsu FanChi,
Shapiro Virginia S.,
Medina Kay L.
Publication year - 2015
Publication title -
immunity, inflammation and disease
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.918
H-Index - 18
ISSN - 2050-4527
DOI - 10.1002/iid3.54
Subject(s) - b cell , b cell activating factor , marginal zone , spleen , adoptive cell transfer , biology , lymphopoiesis , bone marrow , b 1 cell , immunology , knockout mouse , t cell , microbiology and biotechnology , stem cell , receptor , immune system , haematopoiesis , antigen presenting cell , antibody , biochemistry
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.