Junt, T. et al. Subcapsular sinus macrophages in lymph nodes clear lymph-borne viruses and present them to antiviral B cells. Nature 450, 110-114.This study identifies CD169+ macrophages that line the SCS of lymph nodes as essential for the capture of viruses and the initiation of antiviral B-cell responses

Immune Disease Institute and Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Nature (Impact Factor: 41.46). 12/2007; 450(7166):110-4. DOI: 10.1038/nature06287
Source: PubMed


Lymph nodes prevent the systemic dissemination of pathogens such as viruses that infect peripheral tissues after penetrating the body's surface barriers. They are also the staging ground of adaptive immune responses to pathogen-derived antigens. It is unclear how virus particles are cleared from afferent lymph and presented to cognate B cells to induce antibody responses. Here we identify a population of CD11b+CD169+MHCII+ macrophages on the floor of the subcapsular sinus (SCS) and in the medulla of lymph nodes that capture viral particles within minutes after subcutaneous injection. Macrophages in the SCS translocated surface-bound viral particles across the SCS floor and presented them to migrating B cells in the underlying follicles. Selective depletion of these macrophages compromised local viral retention, exacerbated viraemia of the host, and impaired local B-cell activation. These findings indicate that CD169+ macrophages have a dual physiological function. They act as innate 'flypaper' by preventing the systemic spread of lymph-borne pathogens and as critical gatekeepers at the lymph-tissue interface that facilitate the recognition of particulate antigens by B cells and initiate humoral immune responses.

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    • "Presumably, this occurs due to the natural ability of macrophages to express and/or retain Ags for up to 72 h after exposure [57]. Ag are retained due to possible binding of CD169 or MAC1 (macrophage receptor 1) followed by cumulative presentation to respective T and B cells [58] [59]. In the context of particulate-based vaccines, these studies indicate an essential role of macrophages (together with DCs) in the initiation of humoral responses by 1) acting as sentinels at the lymphetissue interface, 2) concentrating Ag in immune tissue (i.e., lymph nodes), and 3) presenting sustained Ag signals. "
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    • "Several studies have focused on the drainage of lymph-borne antigen from the afferent lymph into the subcapsular sinus of the draining LN (Szakal et al., 1983; Carrasco and Batista, 2007; Junt et al., 2007; Phan et al., 2007; Roozendaal et al., 2009; Gonzalez et al., 2010). A current view is that subcapsular sinus macrophages rapidly capture antigen from the lymph and participate in its active transport to the B cell follicle. "
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