Cell extrinsic alterations in splenic B cell maturation in Flt3‐ligand knockout mice

Immunity, Inflammation and Disease

Joseph J. Dolence¹  Kimberly A. Gwin¹  Mariya B. Shapiro¹  Fan-Chi Hsu¹  Virginia S. Shapiro¹ 

[1] Department of Immunology, Mayo Clinic College of Medicine, Rochester, MN

关键词: B lymphopoiesis;    B cell maturation;    BAFF;    Flt3 signaling;    follicular B cells;    marginal zone B cells;    proliferation;    transitional B cells;   

DOI  :  10.1002/iid3.54

来源: Wiley

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2015 The Authors. Immunity, Inflammation and Disease Published by John Wiley & Sons Ltd.

Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.