hsc cmp common lymphoid progenitor prob preb b cd4- cd8- cd4+ gmpmep cd8+ thymus common myeloid...
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HSC
CMP
CommonLymphoidProgenitor
proB preB B
CD4-CD8-
CD4+
GMP
MEP
CD8+
Thymus
Common Myeloid Progenitor
HematopoieticStem Cell
Granulocyte Macrophage
Erythrocyte Megakaryocyte
CD4+ CD8+
immature
Hematopoiesis
IgM IgD
CLP
Thymopoiesis
Thymus
TN3
HSC
44+25- 4+8+
44-25-44+25+
44-25+
4+
8+
TN4TN2
TN1
Myeloid ErythroidCMP
Common Myeloid Progenitor
CD3-CD4-CD8-
(TN, 3-5%)
CD4+CD8+
CD4+CD8+
Common Lymphoid Progenitor
CLP
HSC
CMP
CommonLymphoidProgenitor
proB preB B
CD4-CD8-
CD4+
GMP
MEP
CD8+
Thymus
Common Myeloid Progenitor
HematopoieticStem Cell
Granulocyte Macrophage
Erythrocyte Megakaryocyte
CD4+ CD8+
immature
Hematopoiesis
IgM IgD
CLP
HSC
CMP
CommonLymphoidProgenitor
proB preB B
CD4-CD8-
CD4+
GMP
MEP
CD8+
Thymus
Common Myeloid Progenitor
HematopoieticStem Cell
Granulocyte Macrophage
Erythrocyte Megakaryocyte
CD4+ CD8+
immature
Hematopoiesis
IgM IgD
CLP
Busslinger, M. 2000. Curr. Opinion Immunol. 12:151-158.
Expression of Pax5 is Required for B Lymphopoiesis
HSC
CMP
CommonLymphoidPrecursor
proB preB B
CD4-CD8-
CD4+
GMP
MEP
CD8+
Thymus
Common Myeloid Progenitor
HematopoieticStem Cell
Granulocyte Macrophage
Erythrocyte Megakaryocyte
CD4+ CD8+
immature
Hematopoiesis
IgM IgD
CLP
FACS Resolution of CMP and GMP
Old
CD16/32
Young
CD16/32
CMP
GMP
CD
34
0.19
0.56
0.21
0.38
Gated on Lin-Sca-1-CD127-CD117+
HSC
CLP
CMP
MultipotentlLymphoidPrecursor
proB
GMP
MEP
Common Myeloid Progenitor
HematopoieticStem Cell
Granulocyte Macrophage
Erythrocyte Megakaryocyte
Common Lymphoid Progenitor
CD45RCD43
IgM
immature mature
IgD
Myelopoiesis
preB
ETP
CD4+
CD8+
Thymus
Granulocyte Macrophage Progenitor
Megakaryocyte Erythrocyte Progenitor
Adolfsson et al. Cell 121:295, 2005
Lin- Sca-1+ c-kit+ Flt3+ cells Have B, Granulocyte, and Macrophage Developmental
Potential
HSC
CMP
CommonLymphoidProgenitor
proB preB B
CD4-CD8-
CD4+
GMP
MEP
CD8+
Thymus
Common Myeloid Progenitor
HematopoieticStem Cell
Granulocyte Macrophage
Erythrocyte Megakaryocyte
CD4+ CD8+
immature
Hematopoiesis
IgM IgD
CLP
Adolfsson et al. Cell 121:295, 2005
Lin- Sca-1+ c-kit+ Flt3+ cells Have B, Granulocyte, and Macrophage Developmental
Potential
Adolfsson et al. Cell 121:295, 2005
Lin- Sca-1+ c-kit+ Flt3+ cells Lack Erythroid andMegakaryocyte Developmental Potential
HSC
CMP
CommonLymphoidProgenitor
proB preB B
CD4-CD8-
CD4+
GMP
MEP
CD8+
Thymus
Common Myeloid Progenitor
HematopoieticStem Cell
Granulocyte Macrophage
Erythrocyte Megakaryocyte
CD4+ CD8+
immature
Hematopoiesis
IgM IgD
CLP
Thymopoiesis
Thymus
TN3
HSC
44+25- 4+8+
44-25-44+25+
44-25+
4+
8+
TN4TN2
TN1
Myeloid ErythroidCMP
Common Myeloid Progenitor
CD3-CD4-CD8-
(TN, 3-5%)
CD4+CD8+
CD4+CD8+
Common LymphoidProgenitor
CLP
Lin
CD
44
0.012%
CD127(IL-7Ra)C
D11
7(c
-kit) 0.009%
Based on Allman et al., Nat. Immunol. 4:168, 2003
Isolation of ETP by FACS
HSC
CMP
CommonLymphoidProgenitor
proB preB B
CD4-CD8-
CD4+
GMP
MEP
CD8+
Thymus
Common Myeloid Progenitor
HematopoieticStem Cell
Granulocyte Macrophage
Erythrocyte Megakaryocyte
CD4+ CD8+
immature
Hematopoiesis
IgM IgD
CLP
HSC
CMP
CommonLymphoidPrecursor
proB preB B
CD4-CD8-
CD4+
GMP
MEP
CD8+
Thymus
Common Myeloid Progenitor
HematopoieticStem Cell
Granulocyte Macrophage
Erythrocyte Megakaryocyte
CD4+ CD8+
immature
Adult Hematopoiesis
IgM IgD
CLP
HSC
CMP
GMP
MEP
Common Myeloid Progenitor
HematopoieticStem Cell
Granulocyte Macrophage
Erythrocyte Megakaryocyte
Fetal Hematopoiesis
B
IgM
Pro-B Pre-B
Macrophage
Gekas et al. Developmental Cell 8:365, 2005.
Identification of Hematopoietic Stem Cells in the Placenta
Fetal
Adult
Fetal RBCMyeloid Cells
T cellsB-1 B Cells
Adult RBCMyeloid Cells
B2 B Cells
Fetal Hematopoiesis
B1
B2
B1 and B2 B Cells
IgM
IgMhigh
CD5+/-
CD11b
CD45R
CD45R
IgDlow
IgDhigh
Serous Cavities (peritoneum); self-
renewing; function in innate immunity
Spleen and Lymph Nodes; Produced throughout life;
function in adaptive immunity
Adapted from Rothstein TL. J. Immunol. 168:4257, 2002
Models of B1 B Cell Development
Lineage Selection
B1 Progenitor
B1 Precursor
B2 Progenitor
B2 Precursor
B1 B1B2 B2
B2 Progenitor
B2 Precursor
BCR signals
AGM
Placenta
Melchers, F. Nature 277:219, 1979 d9-11
Paige et al.,J. Exp. Med. 150:548, 1979 d8
Owen, Cooper, & Raff. Nature 249:361, 1974 d12
Solvason et al. Int. Immunol. 3:543, 1991 d13
Velardi, A. and M. Cooper. J. Immunol. 133:672, 1984. d14
Appearance of B Lineage Cells During Embryogenesis
Godin, I. et al. PNAS. 92:773, 1995 d8
AGM
Placenta
Solvason et al. Int. Immunol. 3:543, 1991 d13
Appearance of B Lineage Cells During Embryogenesis
Vosshenrich et al. PNAS 101:11070, 2004
B1 B Cell Numbers Are Reduced In Mice That Fail to Express IL-7R
HSC
CMP
GMP
MEP
Common Myeloid Progenitor
HematopoieticStem Cell
Granulocyte Macrophage
Erythrocyte Megakaryocyte
Fetal Hematopoiesis
B
IgM
Pro-B Pre-B
Macrophage
CD4+
CD8+
T cells
B CELLSMemory B cells
ActivationGerminal center reaction
MZ B cellsSkewed VH repertoire
T CELLSMemory T cells
Activation Oligoclonal dominance
Cytokine productionEffector generation
ThymusBone Marrow
IgM+
B cells
Aging Aging
Spleen
Primary and secondary folliclewith germinal center
Periarteriolar lymphoid sheath
MZ B Cells
Exit of IgM+ cellsT cell
productionAntibody-forming
cells
AgingAging