Different macrophage populations distinguished by means of fluorescent polysaccharides. Recognition and properties of marginal‐zone macrophages

Humphrey, John; Grennan, Deirdre

doi:10.1002/eji.1830110311

Cited by 213 publications

(77 citation statements)

References 11 publications

(3 reference statements)

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“…with dextran-FITC to examine Ag uptake in the spleen. Under normal circumstances, this Ag can rapidly be taken up by MZM, not by MMM, because MZM are highly specific for neutral polysaccharides, such as dextran and Ficoll (26,27). Uptake of this fluorescent Ag was normal in wild-type (WT) mice, but strongly reduced in 4-wk-old CD70TG mice and completely absent in CD70TG mice of 10 wk of age (Fig.…”

Section: Loss Of Mzm Results In Impaired Ag Uptakementioning

confidence: 96%

B Cells Are Crucial for Both Development and Maintenance of the Splenic Marginal Zone

Nolte

Arens²,

Kraus

et al. 2004

The Journal of Immunology

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The splenic marginal zone is a unique compartment that separates the lymphoid white pulp from the surrounding red pulp. Due to the orchestration of specialized macrophages and B cells flanking a marginal sinus, this compartment plays an important role in uptake of blood-borne Ags and it gives the spleen its specialized function in antibacterial immunity. In this study, we demonstrate that both development and maintenance of this marginal zone is highly dependent on the presence of B cells. Spleens from B cell-deficient mice were found to lack both metallophilic and marginal zone macrophages as well as mucosal addressin cellular adhesion molecule-1+ sinus lining cells. Using an inducible Cre/loxP-driven mouse model in which mature B cells could be partially depleted by removal of the B cell receptor subunit Igα, we could show that the integrity and function of an established marginal zone was also dependent on the presence of B cells. This was confirmed in a transgenic model in which all B cells were gradually depleted due to overexpression of the TNF family member CD70. The loss of all cellular subsets from the marginal zone in these CD70 transgenic mice was effectively prevented by crossing these mice on a CD27−/− or TCRα−/− background, because this prohibited the ongoing B cell depletion. Therefore, we conclude that B cells are not only important for the development, but also for maintenance, of the marginal zone. This direct correlation between circulating B cells and the function of the spleen implies an increased risk for B cell lymphopenic patients with bacterial infections.

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Section: Loss Of Mzm Results In Impaired Ag Uptakementioning

confidence: 96%

B Cells Are Crucial for Both Development and Maintenance of the Splenic Marginal Zone

Nolte

Arens²,

Kraus

et al. 2004

The Journal of Immunology

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“…In pioneering studies of the uptake of polysaccharides, primarily dextran, in mouse spleen (33,34), Humphrey and Grennan (33) also reported the uptake of CPS in the macrophages of the marginal zone and red pulp. Recent investigations have shown that the marginal zone macrophages express a C-type lectin, SIGN-R1, that mediates dextran uptake (24,25).…”

Section: Discussionmentioning

confidence: 99%

The C-type lectin SIGN-R1 mediates uptake of the capsular polysaccharide ofStreptococcus pneumoniaein the marginal zone of mouse spleen

Kang

Kim

Bruening

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

180

179

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SIGN-R1, a recently discovered C-type lectin expressed at high levels on macrophages within the marginal zone of the spleen, mediates the uptake of dextran polysaccharides by these phagocytes. We now find that encapsulated Streptococcus pneumoniae are rapidly cleared by these macrophages from the bloodstream, and that capture also takes place when different cell lines express SIGN-R1 after transfection. To assess the role of the capsular polysaccharide of S. pneumoniae (CPS) in the interaction of SIGN-R1 with pneumococci, we first studied binding and uptake of serotype 14 CPS in transfected cells. Binding was observed and was of a much higher avidity (3,000-fold) for CPS 14 than dextran. The CPSs from four different serotypes were also cleared by marginal zone macrophages in vivo. To establish a role for SIGN-R1 in this uptake, we selectively down-regulated expression of the lectin by pretreatment of the mice with SIGN-R1 antibodies, including a newly generated hamster monoclonal called 22D1. For several days after this transient knockout, the marginal zone macrophages were unable to take up either CPSs or dextrans. Therefore, marginal zone macrophages in mice have a receptor that interacts with capsular pneumococcal polysaccharides, setting the stage for further studies of the functional consequences of this interaction.T he spleen functions at several points in innate and adaptive immunity. A major innate function is exerted by macrophages that are abundant in vascular regions termed the splenic red pulp, whereas adaptive functions are carried out by B and T lymphocytes, typically located in white pulp nodules. At the junction of each white pulp nodule with the red pulp is a specialized region called the marginal zone, which is composed of several concentric regions (1). Innermost is a ring of macrophages termed marginal metallophils, expressing a hemagglutinin termed sialoadhesin or CD169 (2, 3). Then there is a vascular sinus that receives blood via penetrating small arterial vessels from the white pulp. Surrounding the marginal sinus is a zone composed of large macrophages as well as specialized B lymphocytes (4). Within and surrounding the marginal zone are also dendritic cells (5, 6), possibly in the process of migrating from the blood to the T cell regions of the white pulp.With respect to host defense, the spleen plays a special role during blood-borne infection with encapsulated microorganisms, particularly Streptococcus pneumoniae bacteria (7-12). A critical role of the spleen is the formation of antibodies by marginal zone B cells (13-15), particularly complement-fixing antibodies (16)(17)(18)(19)(20). The role of macrophages in the processes of microbial clearance and resistance and antibody formation to S. pneumoniae needs to be considered (21), particularly given recent data that marginal zone macrophages interact and retain B cells in this region (22). Here we show that marginal zone macrophages express a receptor called SIGN-R1 that is able to bind and internalize the capsular pneumococcal polys...

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“…T he splenic marginal zone (MZ), 3 defined as the outermost part of the white pulp, represents a microanatomical site populated primarily by B cells and macrophages (1)(2)(3). Splenic MZ B cells are characterized by particular morphologic, cytochemical, and immunophenotypic features (1,4,5).…”

mentioning

confidence: 99%

Heterogeneity of Tonsillar Subepithelial B Lymphocytes, the Splenic Marginal Zone Equivalents

Dono

Zupo²,

Leanza

et al. 2000

The Journal of Immunology

115

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The VH4 genes expressed by both resting and in vivo-activated subepithelial (SE) B cells from human tonsils were studied. Resting SE B cells were subdivided according to the presence (IgDlow) or absence (IgM-only) of surface IgD. CD27 was abundant on activated SE B cells and low on resting IgM-only B cells. Resting IgDlow SE B cells could be subdivided into CD27low and CD27high cell fractions. Resting IgDlow SE B cells displayed VH4 genes with a substantial number of mutations (13/29 of the molecular clones were mutated), whereas 25/26 of the clones from resting IgM-only SE B cells were unmutated. Moreover, mutated VH4 genes were detected mainly within the CD27high cell fraction of the IgDlow SE B cells. Several identical unmutated VH4DJH sequences (11/32) were found in different molecular clones from resting IgM-only SE B cells, suggesting local cellular expansion. Both unmutated (14/25) and mutated (11/25) sequences were found in μ transcripts of activated SE B cells. Extensive mutation was observed in the γ transcripts of activated SE B cells. Therefore, SE B cells are heterogeneous, being comprised of B cells with mutated Ig VH4 genes, that are Ag-experienced B cells, and a subset of B cells with unmutated VH4 genes that are either virgin cells or cells driven by Ags that did not induce or select for V gene mutations.

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Different macrophage populations distinguished by means of fluorescent polysaccharides. Recognition and properties of marginal‐zone macrophages

Cited by 213 publications

References 11 publications

B Cells Are Crucial for Both Development and Maintenance of the Splenic Marginal Zone

B Cells Are Crucial for Both Development and Maintenance of the Splenic Marginal Zone

The C-type lectin SIGN-R1 mediates uptake of the capsular polysaccharide ofStreptococcus pneumoniaein the marginal zone of mouse spleen

Heterogeneity of Tonsillar Subepithelial B Lymphocytes, the Splenic Marginal Zone Equivalents

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