Cell extrinsic alterations in splenic b cell maturation in flt3-ligand knockout mice

Joseph J. Dolence, Kimberly A. Gwin, Mariya B. Shapiro, Fan Chi Hsu, Virginia M Shapiro, Kay L Medina

Research output: Contribution to journalArticle

3 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)103-117
Number of pages15
JournalImmunity Inflammation and Disease
Volume3
Issue number2
DOIs
StatePublished - Jan 1 2015

Fingerprint

Knockout Mice
B-Lymphoid Precursor Cells
B-Lymphocytes
Bone Marrow
B-Cell Activating Factor
Lymphopoiesis
Adoptive Transfer
flt3 ligand protein
Transgenes
Immunity
Up-Regulation
Spleen
Infection
Serum

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

Cite this

Cell extrinsic alterations in splenic b cell maturation in flt3-ligand knockout mice. / Dolence, Joseph J.; Gwin, Kimberly A.; Shapiro, Mariya B.; Hsu, Fan Chi; Shapiro, Virginia M; Medina, Kay L.

In: Immunity Inflammation and Disease, Vol. 3, No. 2, 01.01.2015, p. 103-117.

Research output: Contribution to journalArticle

Dolence, Joseph J. ; Gwin, Kimberly A. ; Shapiro, Mariya B. ; Hsu, Fan Chi ; Shapiro, Virginia M ; Medina, Kay L. / Cell extrinsic alterations in splenic b cell maturation in flt3-ligand knockout mice. In: Immunity Inflammation and Disease. 2015 ; Vol. 3, No. 2. pp. 103-117.
@article{621f9afbf72f4b9794c210349f261256,
title = "Cell extrinsic alterations in splenic b cell maturation in flt3-ligand knockout mice",
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.",
keywords = "B cell maturation, B lymphopoiesis, BAFF, Flt3 signaling, Follicular B cells, Marginal zone B cells, Proliferation, Transitional B cells",
author = "Dolence, {Joseph J.} and Gwin, {Kimberly A.} and Shapiro, {Mariya B.} and Hsu, {Fan Chi} and Shapiro, {Virginia M} and Medina, {Kay L}",
year = "2015",
month = "1",
day = "1",
doi = "10.1002/iid3.54",
language = "English (US)",
volume = "3",
pages = "103--117",
journal = "Immunity, inflammation and disease",
issn = "2050-4527",
publisher = "John Wiley and Sons Ltd",
number = "2",

}

TY - JOUR

T1 - Cell extrinsic alterations in splenic b cell maturation in flt3-ligand knockout mice

AU - Dolence, Joseph J.

AU - Gwin, Kimberly A.

AU - Shapiro, Mariya B.

AU - Hsu, Fan Chi

AU - Shapiro, Virginia M

AU - Medina, Kay L

PY - 2015/1/1

Y1 - 2015/1/1

N2 - 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.

AB - 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.

KW - B cell maturation

KW - B lymphopoiesis

KW - BAFF

KW - Flt3 signaling

KW - Follicular B cells

KW - Marginal zone B cells

KW - Proliferation

KW - Transitional B cells

UR - http://www.scopus.com/inward/record.url?scp=85019292284&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85019292284&partnerID=8YFLogxK

U2 - 10.1002/iid3.54

DO - 10.1002/iid3.54

M3 - Article

VL - 3

SP - 103

EP - 117

JO - Immunity, inflammation and disease

JF - Immunity, inflammation and disease

SN - 2050-4527

IS - 2

ER -