Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 1999 Jan 4;189(1):159-68.
doi: 10.1084/jem.189.1.159.

Mature follicular dendritic cell networks depend on expression of lymphotoxin beta receptor by radioresistant stromal cells and of lymphotoxin beta and tumor necrosis factor by B cells

Affiliations

Mature follicular dendritic cell networks depend on expression of lymphotoxin beta receptor by radioresistant stromal cells and of lymphotoxin beta and tumor necrosis factor by B cells

R Endres et al. J Exp Med. .

Abstract

The formation of germinal centers (GCs) represents a crucial step in the humoral immune response. Recent studies using gene-targeted mice have revealed that the cytokines tumor necrosis factor (TNF), lymphotoxin (LT) alpha, and LTbeta, as well as their receptors TNF receptor p55 (TNFRp55) and LTbetaR play essential roles in the development of GCs. To establish in which cell types expression of LTbetaR, LTbeta, and TNF is required for GC formation, LTbetaR-/-, LTbeta-/-, TNF-/-, B cell-deficient (BCR-/-), and wild-type mice were used to generate reciprocal or mixed bone marrow (BM) chimeric mice. GCs, herein defined as peanut agglutinin-binding (PNA+) clusters of centroblasts/centrocytes in association with follicular dendritic cell (FDC) networks, were not detectable in LTbetaR-/- hosts after transfer of wild-type BM. In contrast, the GC reaction was restored in LTbeta-/- hosts reconstituted with either wild-type or LTbetaR-/- BM. In BCR-/- recipients reconstituted with compound LTbeta-/-/BCR-/- or TNF-/-/BCR-/- BM grafts, PNA+ cell clusters formed in splenic follicles, but associated FDC networks were strongly reduced or absent. Thus, development of splenic FDC networks depends on expression of LTbeta and TNF by B lymphocytes and LTbetaR by radioresistant stromal cells.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Splenic GC development in reciprocal BM chimeric mice. Irradiated recipients (n = 3–5 per group) were reconstituted with BM from donors as indicated. After 8 wk, chimeras were immunized intraperitoneally with 5 μg NP19-CG adsorbed to alum. 10 d later, chimeras were killed and splenic cryosections were labeled with anti-CR1 (brown) and PNA (blue); anti-B220 (brown) and PNA (blue); or anti-CD4 (brown), anti-CD8 (brown), and anti-IgD (blue).
Figure 2
Figure 2
Splenic GC development in compound BM chimeric mice. Irradiated recipients (n = 4 per group) were reconstituted with a 1:1 mixture of BM cells originating from the two donors indicated. After 6–7 wk, the mixed BM chimeras were immunized intraperitoneally with 5 μg NP19-CG adsorbed to alum. 10 d later, chimeras were killed and splenic cryosections were labeled with anti-CR1 (brown) and PNA (blue); anti-B220 (brown) and PNA (blue); or anti-CD4 (brown), anti-CD8 (brown), and anti-IgD (blue).
Figure 3
Figure 3
NP-specific IgG titers in the sera of reciprocal (A and B) and mixed BM chimeras (C and D). Chimeric mice were made and immunized as described in the legends to Figs. 1 and 2 (n = 3–5 per group). Sera were taken before and 10 d after immunization. The amounts of anti-NP antibodies were determined as described in Materials and Methods. Note that two different batches of NP19-CG adsorbed to alum were used for immunization, precluding a direct comparison of values from A and B with those from C and D. •, All values were below the detection limit.
Figure 4
Figure 4
Model of the molecular interactions essential for the establishment of splenic FDC networks associated with PNA+ cell clusters. B cells provide the ligands LTα (references 28, 29), TNF, and LTβ required for an effective engagement of the TNFRp55 (references 25, 26) and the LTβR on specific radioresistant cells, which most likely represent FDC precursors. In this cell population, both signaling pathways have to be functional for mature splenic FDC networks to form. Note that the present data do not elucidate whether signaling from the TNFRp55 and the LTβR has to occur simultaneously or consecutively in the putative FDC precursors. TNFRI, TNFRp55.

Similar articles

Cited by

References

    1. Kosco-Vilbois MH, Bonnefoy JY, Chvatchko Y. The physiology of murine germinal center reactions. Immunol Rev. 1997;156:127–136. - PubMed
    1. Kelsoe G, Zheng B. Sites of B-cell activation in vivo. Curr Opin Immunol. 1993;5:418–422. - PubMed
    1. MacLennan IC. Germinal centers. Annu Rev Immunol. 1994;12:117–139. - PubMed
    1. Tew JG, Wu J, Qin D, Helm S, Burton GF, Szakal AK. Follicular dendritic cells and presentation of antigen and costimulatory signals to B cells. Immunol Rev. 1997;156:39–52. - PubMed
    1. Liu YJ, Arpin C. Germinal center development. Immunol Rev. 1997;156:111–126. - PubMed

Publication types

MeSH terms