RESUMO
The developmental biology of dendritic cells (DC) under physiological conditions remains unclear. In this study, we show that mouse CD11c(+) MHC class II(-)lineage(-) cells are immediate precursors of conventional DC and are widely distributed in both bone marrow and lymphoid tissues. These precursors have a high clonal efficiency, and when cocultured on a supportive stromal monolayer or adoptively transferred in vivo, generate a population CD11c(+)MHC class II(+) DC that retain limited proliferation capacity. During steady state conditions, a small proportion of immediate DC precursors (DCp) and DCs are dividing actively in bone marrow and spleen. Cytokines that initiate and support proliferation of immediate DCp were defined. Collectively, our findings provide evidence of a distinct development pathway for conventional DC in both bone marrow and lymphoid tissues and highlight the importance of in situ replication of immediate DCp and DC in maintaining conventional DC populations.
Assuntos
Divisão Celular/imunologia , Células Dendríticas/citologia , Células Dendríticas/imunologia , Homeostase/imunologia , Tecido Linfoide/citologia , Tecido Linfoide/imunologia , Células-Tronco/citologia , Células-Tronco/imunologia , Animais , Células da Medula Óssea/citologia , Células da Medula Óssea/imunologia , Células da Medula Óssea/metabolismo , Diferenciação Celular/imunologia , Proliferação de Células , Células Cultivadas , Células Clonais , Células Dendríticas/metabolismo , Antígenos Comuns de Leucócito/metabolismo , Tecido Linfoide/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Transdução de Sinais/imunologia , Baço/citologia , Baço/imunologia , Baço/metabolismo , Células-Tronco/metabolismoRESUMO
The developmental pathways and differentiation relationship of dendritic cell (DC) subsets remain unclear. We report that murine CD11c(+)MHC II(-) bone marrow cells, which are immediate DC precursors of CD8 alpha(+), CD8 alpha(-), and B220(+) DC in vivo, can be separated into B220(+) and B220(-) DC precursor subpopulations. Purified B220(-) DC precursors expand, and generate exclusively mature CD11c(+)CD11b(+)B220(-) DC in vitro and after adoptive transfer. B220(+) DC precursors, which resemble plasmacytoid pre-DC, have a lower proliferative potential than B220(-) DC precursors and generate both CD11b(-) B220(+) and CD11b(+)B220(-) DC populations. Both DC precursor populations can give rise to CD8 alpha(+) and CD8 alpha(-) DC subtypes. Our findings indicate that CD11c(+)MHC II(-)B220(+) and CD11c(+)MHC II(-)B220(-) bone marrow cells are distinct DC lineage-restricted precursors.
Assuntos
Células da Medula Óssea/citologia , Células Dendríticas/citologia , Transferência Adotiva , Animais , Animais Congênicos , Antígeno CD11c/análise , Diferenciação Celular , Divisão Celular , Linhagem da Célula , Separação Celular , Células Cultivadas , Ilhas de CpG/imunologia , Células Dendríticas/efeitos dos fármacos , Células Dendríticas/imunologia , Feminino , Citometria de Fluxo , Antígenos de Histocompatibilidade Classe II/análise , Antígenos Comuns de Leucócito/análise , Lipopolissacarídeos/farmacologia , Teste de Cultura Mista de Linfócitos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Quimera por Radiação , Organismos Livres de Patógenos EspecíficosRESUMO
The engraftment of murine hematopoietic stem cells (HSCs) into irradiated mice is thought to be an inefficient process, but has yet to be measured directly. We used two independent strategies to test their engraftment efficiency: one measured competition of unpurified donor bone marrow cells with recipient cells in murine hosts and the other tracked the engraftment of one highly purified stem cell injected per recipient. The results showed that stem cells engrafted with near absolute efficiency. Thus, inefficient engraftment cannot explain the low frequency of permanent reconstitutions observed with pure HSC fractions and instead suggests most initially engrafted cells fail to sustain self-renewal.