1 / 19

Role of Bone Marrow Dendritic Cells in B Cell Survival Signals

Explore how perivascular clusters of dendritic cells support B cell survival in bone marrow niches, impacting humoral immune responses and mature B cell maintenance. Understand the phenotypic characterization and functional significance of bone marrow-resident dendritic cells.

elsea
Download Presentation

Role of Bone Marrow Dendritic Cells in B Cell Survival Signals

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Perivascular clusters of dendritic cells provide critical survival signals to B cells in bone marrow niches Anita Sapoznikov et al. Nature immunology 2008; March 2

  2. Background • The bone marrow is generally considered a primary lymphoid organ that provides a unique microenvironment with defined niches for stem cells, lymphogenesis and myelogenesis. • Early B cell development is confined to the bone marrow, immature B cells then leave the bone marrow and mature in the spleen. • Notably, up to a quarter of the mature B cell pool positive for IgD and IgM can be found recirculating in the steady state through the bone marrow. • Moreover, bone marrow–resident mature B cells can participate in situ in T cell–independent humoral immune responses to blood-borne microbes.

  3. Background • Bone marrow constitutes a storage site for terminally differentiated B cells. • Mature CD4+ and CD8+ T cells continuously home to the bone marrow. • Bone marrow represents a principal reservoir for both CD4+ and CD8+ memory T cells. • Bone marrow–resident naive and memory T cells can both be activated in situ, which suggests the presence of ‘professional’ antigen-presenting cells in the bone marrow.

  4. Question • What is the phenotypic characterization and function of bone marrow–resident DCs (bmDCs)?

  5. Characterization of bmDCs

  6. Organization of bmDCs into perivascular clusters

  7. Two-photon microscopy of cranial bone marrow cavities of x3cr1gfp/+ mice (bmDCs, green; blood vessels, red)

  8. Two-photon microscopy of the colocalization of adoptively transferred B ,T cells, host bmDCs and blood vessels in the bone marrow cavity of a Cx3cr1gfp/+ mouse

  9. Conditional ablation of bmDCs

  10. Ablation of bmDCs causes loss of recirculating B cells

  11. The bmDCs provide a survival signal to mature B cells

  12. The survival of mature B cells in bone marrow is independent of BAFF-producing bmDCs

  13. B cells require MIF-producing bmDCs for survival Flow cytometry of mature B cells in the bone marrow for surface expression of CD44 and CD74, components of the MIF receptor complex

  14. B220+CD93–CD23+ mature cells from the spleens and bone marrow of Mif –/– mice and wild-type control mice

  15. splenic DCs in control wild-type mice reconstituted with bone marrow from Mif –/– mice and CD11c-DTRtg mice (Mif –/–;DTRtg-WT)

  16. bone marrow and spleen B cell compartments of the following bone marrow chimeras: wild-typemice reconstituted with bone marrow from CD11c-DTRtg mice (DTRtg-WT), from Mif –/– mice and CD11c-DTRtg mice (Mif –/–DTRtg-WT) or from Baff –/– mice and CD11c-DTRtg mice (Baff –/–DTRtg-WT)

  17. distribution of Mif –/– B cells (CD45.1–) and Mif +/+ B cells (CD45.1+) in the bone marrow B cell compartment.

More Related