The dual function of the splenic marginal zone: essential for initiation of anti-TI-2 responses but also vital in the general first-line defense against blood-borne antigens

Zandvoort, Andre; Timens, Wim

doi:10.1046/j.1365-2249.2002.01953.x

Cited by 191 publications

(153 citation statements)

References 57 publications

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“…As marginal zone B cells are believed to be important for T-independent type-2 responses [22], immunization with NP-Ficoll was performed in the different mice. As expected, antibody titers obtained were comparable in wild-type and Bcl-2-Tg mice, but were much reduced in TACI-Ig-Tg mice (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…In marginal zone B cells, its engagement by blood-borne antigens opsonized with C3d is believed to provide the basis for T-independent type-2 antibody responses, in particular of IgG2a and IgG3 isotypes [22,34]. The impaired IgG3 response to NP-Ficoll in TACI-Ig×Bcl-2 dTg mice is consistent with their lack of marginal zone B cells and is comparable to that observed in the marginal zone B cell-deficient Pyk-2 -/-mice [34].…”

Section: Discussionmentioning

confidence: 99%

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The anti‐apoptotic factor Bcl‐2 can functionally substitute for the B cell survival but not for the marginal zone B cell differentiation activity of BAFF

et al. 2004

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The TNF family ligand B cell-activating factor (BAFF, BLyS, TALL-1) is an essential factor for B cell development. BAFF binds to three receptors, BAFF-R, transmembrane activator and CAML interactor (TACI), and B cell maturation antigen (BCMA), but only BAFF-R is required for successful survival and maturation of splenic B cells. To test whether the effect of BAFF is due to the up-regulation of anti-apoptotic factors, TACI-Ig-transgenic mice, in which BAFF function is inhibited, were crossed with transgenic mice expressing FLICE-inhibitory protein (FLIP) or Bcl-2 in the B cell compartment. FLIP expression did not rescue B cells, while enforced Bcl-2 expression restored peripheral B cells and the ability to mount T-dependent antibody responses. However, many B cells retained immaturity markers and failed to express normal amounts of CD21. Marginal zone B cells were not restored and the Tindependent IgG3, but not IgM, response was impaired in the TACI-Ig×Bcl-2 mice. These results suggest that BAFF is required not only to inhibit apoptosis of maturating B cells, but also to promote differentiation events, in particular those leading to the generation of marginal zone B cells.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

The anti‐apoptotic factor Bcl‐2 can functionally substitute for the B cell survival but not for the marginal zone B cell differentiation activity of BAFF

et al. 2004

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“…With respect to host defense, the spleen plays a special role during blood-borne infection with encapsulated microorganisms, particularly Streptococcus pneumoniae bacteria (7)(8)(9)(10)(11)(12). A critical role of the spleen is the formation of antibodies by marginal zone B cells (13)(14)(15), particularly complement-fixing antibodies (16)(17)(18)(19)(20).…”

mentioning

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.

182

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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“…The splenic marginal zone is the important substructure because it efficiently and quickly captures, presents and relocates to the germinal centers T-dependent and Tindependent immunogens and other blood-borne antigens [73][74][75]. In term-newborns, the spleen shows no evidence of a marginal zone [54].…”

Section: Maturation Of the Immune Response To Polysaccharide Vaccinesmentioning

confidence: 99%

The role of complement in the success of vaccination with conjugated vs. unconjugated polysaccharide antigen

Salehen¹,

Stover²

2008

Vaccine

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The complement system, a well-characterised arm of the innate immune system, significantly influences the adaptive immune response via direct cell-cell interaction and maintenance of lymphoid organ architecture. Development of vaccines is a major advance in modern health care. In this review, we highlight the importance of the marginal zone in response to both, polysaccharide and conjugated vaccines, and discuss the relevance of complement herein, based on findings obtained from animal models with specific deletions of certain complement components and from vaccination reports of complement-deficient individuals. We conclude that both, intactness of the complement system and maturity of expression of its components, are relatively more important to aid in the immune response to polysaccharide vaccine than to conjugated vaccines. keywords (3): complement vaccine polysaccharide running titleComplement essential for polysaccharide vaccines 2 The importance of complement activation in adaptive immunityThe complement system is part of the innate immune defence, because it partakes in first-line, pattern-mediated recognition via its germ-line encoded serum proteins and receptors. It has evolved from a primordial fluid-phase system that "simply" tags and mediates uptake of micro-organisms by cells of early chordates. Large-scale gene duplications, exon shuffling and transposition events are the main evolutionary mechanisms that have generated a wide range of diversified molecules, which we now ascribe to innate and adaptive immune defences Importantly, after subcutaneous administration of T-independent or T-dependent antigens in mice, it is the spleen that reacts with formation of antibody forming cells before the draining lymphnodes, especially in response to T-independent antigen [32].Germinal centers are formed during an immune response elicited with a so-called Tindependent antigen. This reaction is, however, of short duration. It is possible that the absence of somatic hypermutation of the immunoglobulin V genes is due to both, the curtailed germinal center reaction -as somatic hypermutation is a relatively late event -6 and the lack of T-cell help [33]. Of note, marginal zone B-cells are incapable of participating in the process of somatic hypermutation due to the lack of expression of activation-induced cytidine deaminase, an enzyme essential for this process [34].The involvement of T-cells is not strictly excluded in the antibody response against polysaccharides, as B7 ligand dependent costimulation of B-cells (by T-cells) is needed, however, the interaction in this early response is short and T-cell receptor unspecific [35].The absence of somatic hypermutation does, however, explain the low affinity binding of anti-polysaccharide antibodies.

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The dual function of the splenic marginal zone: essential for initiation of anti-TI-2 responses but also vital in the general first-line defense against blood-borne antigens

Cited by 191 publications

References 57 publications

The anti‐apoptotic factor Bcl‐2 can functionally substitute for the B cell survival but not for the marginal zone B cell differentiation activity of BAFF

The anti‐apoptotic factor Bcl‐2 can functionally substitute for the B cell survival but not for the marginal zone B cell differentiation activity of BAFF

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

The role of complement in the success of vaccination with conjugated vs. unconjugated polysaccharide antigen

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