The follicular dendritic cell restricted epitope, FDC-M2, is complement C4; localization of immune complexes in mouse tissues

Taylor, Philip R.; Pickering, Matthew C.; Kosco‐Vilbois, Marie H.; Walport, Mark J.; Botto, Marina; Gordon, Siamon; Martı́nez-Pomares, Luisa

doi:10.1002/1521-4141(200207)32:7<1883::aid-immu1888>3.0.co;2-8

Cited by 60 publications

(54 citation statements)

References 26 publications

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“…Although this statement may appear a contradiction, it is experimentally validated: in 2003, Rahman et al (23) showed that all splenic GCs of SRBC-immunized A/J and C57BL/6 mice stain extensively for Ki-67. In agreement with FDC-M2 is a well-established and widely used FDC marker that is also lowly expressed on white pulp reticular cells and some uncharacterized perivascular cells (37). However, the latter does not interfere with detection of FDC networks or other GC cell populations.…”

Section: Identification Of Gcssupporting

confidence: 63%

Is There a Typical Germinal Center? A Large-Scale Immunohistological Study on the Cellular Composition of Germinal Centers during the Hapten-Carrier–Driven Primary Immune Response in Mice

Wittenbrink

Klein

Weiser

et al. 2011

The Journal of Immunology

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Germinal centers (GCs) are complex, multicell-type, transient structures that form in secondary lymphatic tissues in response to T cell-dependent stimulation. This process is crucial to the adaptive immune response because it is the source of affinity maturation and long-lived B cell memory. Our previous studies showed that the growth of murine splenic GCs is nonsynchronized, involving broad-volume distributions of individual GCs at any time. This raises the question whether such a thing as a typical GC exists. To address this matter, we acquired large-scale confocal data on GCs throughout the course of the 2-phenyl-5-oxazolone chicken serum albumin-driven primary immune response in BALB/c mice. Semiautomated image analysis of 3457 GC sections revealed that, although there is no typical GC in terms of size, GCs have a typical cellular composition in that the cell ratios of resident T cells, macrophages, proliferating cells, and apoptotic nuclei are maintained during the established phase of the response. Moreover, our data provide evidence that the dark zone (DZ) and light zone (LZ) compartments of GCs are about the same size and led us to estimate that the minimal cell loss rate in GCs is 3% per hour. Furthermore, we found that the population of GC macrophages is larger and more heterogeneous than previously thought, and that despite enrichment of T cells in the LZ, the DZ of murine splenic GCs is not poor in T cells. DZ and LZ differ in the T cell-to-macrophage ratio rather than in the density of T cells.

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Section: Identification Of Gcssupporting

confidence: 63%

Is There a Typical Germinal Center? A Large-Scale Immunohistological Study on the Cellular Composition of Germinal Centers during the Hapten-Carrier–Driven Primary Immune Response in Mice

Wittenbrink

Klein

Weiser

et al. 2011

The Journal of Immunology

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“…Recent studies have identified the antigen recognized by the FDC-specific antiserum FDC-M2 as complement component C4 (55). Thus, the temporary loss of FDC-M2-specific immunostaining after treatment with LT␤R-Ig is also consistent with the inability of these cells to trap and retain complementopsonized antigens.…”

mentioning

confidence: 86%

Follicular Dendritic Cell Dedifferentiation by Treatment with an Inhibitor of the Lymphotoxin Pathway Dramatically Reduces Scrapie Susceptibility

Mabbott

Young

McConnell

et al. 2003

J Virol

141

178

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“…Control conditions included B cells alone, B cells plus anti-IgD mAb, B cells plus anti-IgD ICs, and B cells plus antiIgD mAb plus FDCs. FDC-M2 is a rat anti-mouse mAb that detects an epitope of C4 localized to the ICs trapped on FDCs (21,32). This anti-C4 appears to block C4-BP, which is capable of interacting with CD40 on B cells (21).…”

Section: Assessment Of Fdc-baff Production and The Effect Of Neutralimentioning

confidence: 99%

T-Independent Antibody Responses to T-Dependent Antigens: A Novel Follicular Dendritic Cell-Dependent Activity

Shikh

Sayed²,

Szakal³

et al. 2009

The Journal of Immunology

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Follicular dendritic cells (FDCs) periodically arrange membrane-bound immune complexes (ICs) of T-dependent Ags 200–500Å apart, and in addition to Ag, they provide B cells with costimulatory signals. This prompted the hypothesis that Ag in FDC-ICs can simultaneously cross-link multiple BCRs and induce T cell-independent (TI) B cell activation. TI responses are characterized by rapid IgM production. OVA-IC-bearing FDCs induced OVA-specific IgM in anti-Thy-1-pretreated nude mice and by purified murine and human B cells in vitro within just 48 h. Moreover, nude mice immunized with OVA-ICs exhibited well-developed GL-7+ germinal centers with IC-retaining FDC-reticula and Blimp-1+ plasmablasts within 48 h. In contrast, FDCs with unbound-OVA, which would have free access to BCRs, induced no germinal centers, plasmablasts, or IgM. Engagement of BCRs with rat-anti-mouse IgD (clone 11–26) does not activate B cells even when cross-linked. However, B cells were activated when anti-IgD-ICs, formed with Fc-specific rabbit anti-rat IgG, were loaded on FDCs. B cell activation was indicated by high phosphotyrosine levels in caps and patches, expression of GL-7 and Blimp-1, and B cell proliferation within 48 h after stimulation with IC-bearing FDCs. Moreover, anti-IgD-IC-loaded FDCs induced strong polyclonal IgM responses within 48 h. Blockade of FDC-FcγRIIB inhibited the ability of FDC-ICs to induce T-independent IgM responses. Similarly, neutralizing FDC-C4BP or -BAFF, to minimize these FDC-costimulatory signals, also inhibited this FDC-dependent IgM response. This is the first report of FDC-dependent but TI responses to T cell-dependent Ags.

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The follicular dendritic cell restricted epitope, FDC-M2, is complement C4; localization of immune complexes in mouse tissues

Cited by 60 publications

References 26 publications

Is There a Typical Germinal Center? A Large-Scale Immunohistological Study on the Cellular Composition of Germinal Centers during the Hapten-Carrier–Driven Primary Immune Response in Mice

Is There a Typical Germinal Center? A Large-Scale Immunohistological Study on the Cellular Composition of Germinal Centers during the Hapten-Carrier–Driven Primary Immune Response in Mice

Follicular Dendritic Cell Dedifferentiation by Treatment with an Inhibitor of the Lymphotoxin Pathway Dramatically Reduces Scrapie Susceptibility

T-Independent Antibody Responses to T-Dependent Antigens: A Novel Follicular Dendritic Cell-Dependent Activity

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