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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.

Endres R, Alimzhanov MB, Plitz T, Fütterer A, Kosco-Vilbois MH, Nedospasov SA, Rajewsky K, Pfeffer K - J. Exp. Med. (1999)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Institute of Medical Microbiology, Immunology and Hygiene, Technical University of Munich, D-81675 Munich, Germany.

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.

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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.
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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.

Mentions: To investigate whether the observed abnormal GC reactions correlated with impaired specific IgG responses, NP-specific IgG titers were quantified in the sera of animals 10 d after immunization. Densely or sparsely haptenated BSA (NP12-BSA or NP5-BSA) was used for coating of ELISA plates, allowing detection of both low and high affinity NP-specific IgG. B6 → B6 and LTβR−/− → B6 chimeras responded to immunization with a comparable production of specific IgG, whereas B6 → LTβR−/− animals did not mount a significant primary IgG response (Fig. 3, A and B). Moreover, significant defects were not observed in B6 → LTβ−/−, LTβ−/− → B6, or LTβR−/− → LTβ−/− chimeras (data not shown). In B6 → LTβR−/− chimeras, the impaired primary IgG response correlated with multiple defects in the organization of peripheral lymphoid tissues such as lack of lymph nodes and Peyer's patches, disruption of T–B cell segregation, and aberrant PNA+ cell clusters without FDC networks in the spleen (macroscopic examination, and Fig. 1, E–H). In contrast, LTβ−/− + BCR−/− → BCR−/− and TNF−/− + BCR−/− → BCR−/− mice contained lymph nodes, PNA+ cell clusters, and distinct T and B cell areas, yet differed from their control groups regarding splenic FDC network formation (Fig. 2). Here, differences in NP-specific IgG titers between experimental and control groups were not statistically significant (Fig. 3, C and D), implying that a lack or strong reduction of splenic FDC networks does not necessarily lead to impaired specific primary IgG responses.


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.

Endres R, Alimzhanov MB, Plitz T, Fütterer A, Kosco-Vilbois MH, Nedospasov SA, Rajewsky K, Pfeffer K - J. Exp. Med. (1999)

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.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC1887694&req=5

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.
Mentions: To investigate whether the observed abnormal GC reactions correlated with impaired specific IgG responses, NP-specific IgG titers were quantified in the sera of animals 10 d after immunization. Densely or sparsely haptenated BSA (NP12-BSA or NP5-BSA) was used for coating of ELISA plates, allowing detection of both low and high affinity NP-specific IgG. B6 → B6 and LTβR−/− → B6 chimeras responded to immunization with a comparable production of specific IgG, whereas B6 → LTβR−/− animals did not mount a significant primary IgG response (Fig. 3, A and B). Moreover, significant defects were not observed in B6 → LTβ−/−, LTβ−/− → B6, or LTβR−/− → LTβ−/− chimeras (data not shown). In B6 → LTβR−/− chimeras, the impaired primary IgG response correlated with multiple defects in the organization of peripheral lymphoid tissues such as lack of lymph nodes and Peyer's patches, disruption of T–B cell segregation, and aberrant PNA+ cell clusters without FDC networks in the spleen (macroscopic examination, and Fig. 1, E–H). In contrast, LTβ−/− + BCR−/− → BCR−/− and TNF−/− + BCR−/− → BCR−/− mice contained lymph nodes, PNA+ cell clusters, and distinct T and B cell areas, yet differed from their control groups regarding splenic FDC network formation (Fig. 2). Here, differences in NP-specific IgG titers between experimental and control groups were not statistically significant (Fig. 3, C and D), implying that a lack or strong reduction of splenic FDC networks does not necessarily lead to impaired specific primary IgG responses.

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Institute of Medical Microbiology, Immunology and Hygiene, Technical University of Munich, D-81675 Munich, Germany.

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.

Show MeSH
Related in: MedlinePlus