Context-Dependent Development of Lymphoid Stroma from Adult CD34(+) Adventitial Progenitors

Katarzyna M Sitnik; Kerstin Wendland; Holger Weishaupt; Heli Uronen-Hansson; Andrea J White; Graham Anderson; Knut Kotarsky; William W Agace

doi:10.1016/j.celrep.2016.02.033

Context-Dependent Development of Lymphoid Stroma from Adult CD34(+) Adventitial Progenitors

Cell Rep. 2016 Mar 15;14(10):2375-88. doi: 10.1016/j.celrep.2016.02.033. Epub 2016 Mar 3.

Authors

Katarzyna M Sitnik¹, Kerstin Wendland², Holger Weishaupt³, Heli Uronen-Hansson², Andrea J White⁴, Graham Anderson⁴, Knut Kotarsky², William W Agace⁵

Affiliations

¹ Section for Immunology and Vaccinology, National Veterinary Institute, Technical University of Denmark, Bülowsvej 27, 1870 Frederiksberg C, Denmark. Electronic address: [email protected].
² Immunology Section, Lund University, BMC D14, 221-84 Lund, Sweden.
³ Department of Immunology, Genetics, and Pathology, Rudbecklaboratoriet, Uppsala University, 751-85 Uppsala, Sweden.
⁴ Medical Research Council Centre for Immune Regulation, Institute for Biomedical Research, University of Birmingham, Birmingham B15 2TT, UK.
⁵ Section for Immunology and Vaccinology, National Veterinary Institute, Technical University of Denmark, Bülowsvej 27, 1870 Frederiksberg C, Denmark; Immunology Section, Lund University, BMC D14, 221-84 Lund, Sweden. Electronic address: [email protected].

PMID: 26947077
DOI: 10.1016/j.celrep.2016.02.033

Abstract

Despite the key role of primary and secondary lymphoid organ stroma in immunity, our understanding of the heterogeneity and ontogeny of these cells remains limited. Here, we identify a functionally distinct subset of BP3(-)PDPN(+)PDGFRβ(+)/α(+)CD34(+) stromal adventitial cells in both lymph nodes (LNs) and thymus that is located within the vascular niche surrounding PDPN(-)PDGFRβ(+)/α(-)Esam-1(+)ITGA7(+) pericytes. CD34(+) adventitial cells developed in late embryonic thymus and in postnatal LNs and in the thymus originated, along with pericytes, from a common anlage-seeding progenitor population. Using lymphoid organ re-aggregate grafts, we demonstrate that adult CD34(+) adventitial cells are capable of differentiating into multiple lymphoid stroma-like subsets including pericyte-, FRC-, MRC-, and FDC-like cells, the development of which was lymphoid environment-dependent. These findings extend the current understanding of lymphoid mesenchymal cell heterogeneity and highlight a role of the CD34(+) adventitia as a potential ubiquitous source of lymphoid stromal precursors in postnatal tissues.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

ADP-ribosyl Cyclase / genetics
ADP-ribosyl Cyclase / metabolism
Animals
Antigens, CD / genetics
Antigens, CD / metabolism
Antigens, CD34 / metabolism*
Cell Differentiation
Cells, Cultured
Embryo, Mammalian / cytology
Embryo, Mammalian / metabolism
Flow Cytometry
GPI-Linked Proteins / genetics
GPI-Linked Proteins / metabolism
Immunohistochemistry
Lymph Nodes / cytology
Lymph Nodes / metabolism
Lymphotoxin beta Receptor / deficiency
Lymphotoxin beta Receptor / genetics
Lymphotoxin beta Receptor / metabolism
Membrane Glycoproteins / genetics
Membrane Glycoproteins / metabolism
Mice
Mice, Inbred C57BL
Mice, Knockout
Pericytes / cytology
Pericytes / metabolism
Receptor, Platelet-Derived Growth Factor beta / genetics
Receptor, Platelet-Derived Growth Factor beta / metabolism
Signal Transduction
Stromal Cells / cytology
Stromal Cells / metabolism*
Thymus Gland / cytology
Thymus Gland / metabolism

Substances

Antigens, CD
Antigens, CD34
GPI-Linked Proteins
Gp38 protein, mouse
Ltbr protein, mouse
Lymphotoxin beta Receptor
Membrane Glycoproteins
Receptor, Platelet-Derived Growth Factor beta
ADP-ribosyl Cyclase
ADP-ribosyl cyclase 2

Grants and funding

MR/N000919/1/MRC_/Medical Research Council/United Kingdom