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Viral superantigen drives extrafollicular and follicular B cell differentiation leading to virus-specific antibody production.

Luther SA, Gulbranson-Judge A, Acha-Orbea H, MacLennan IC - J. Exp. Med. (1997)

Bottom Line: The response to MMTV(SW) in draining lymph nodes was compared with the response to haptenated chicken gamma globulin (NP-CGG) using flow cytometry and immunohistology.Germinal centers develop in both responses, but those induced by MMTV(SW) appear later and are smaller.Most T cells activated in the T zone and germinal centers in the MMTV(SW) response are superantigen specific and these persist for weeks in lymph nodes draining the site MMTV(SW) injection: this contrasts with the selective loss of superantigen-specific T cells from other secondary lymphoid tissues.

View Article: PubMed Central - PubMed

Affiliation: Ludwig Institute for Cancer Research, University of Lansanne, Epalinges.

ABSTRACT
Mouse mammary tumor virus (MMTV[SW]) encodes a superantigen expressed by infected B cells. It evokes an antibody response specific for viral envelope protein, indicating selective activation of antigen-specific B cells. The response to MMTV(SW) in draining lymph nodes was compared with the response to haptenated chicken gamma globulin (NP-CGG) using flow cytometry and immunohistology. T cell priming occurs in both responses, with T cells proliferating in association with interdigitating dendritic cells in the T zone. T cell proliferation continues in the presence of B cells in the outer T zone, and B blasts then undergo exponential growth and differentiation into plasma cells in the medullary cords. Germinal centers develop in both responses, but those induced by MMTV(SW) appear later and are smaller. Most T cells activated in the T zone and germinal centers in the MMTV(SW) response are superantigen specific and these persist for weeks in lymph nodes draining the site MMTV(SW) injection: this contrasts with the selective loss of superantigen-specific T cells from other secondary lymphoid tissues. The results indicate that this viral superantigen, when expressed by professional antigen-presenting cells, drives extrafollicular and follicular B cell differentiation leading to virus-specific antibody production.

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Photomicrographs  of stained sections to show germinal centers formed during responses to NP-CGG in a and  MMTV(SW) in b–d within the  draining LN. a (×250) shows a  LN taken 8 d after immunization  with NP-CGG stained for IgD  (brown), CD3 (blue) and BrdU  (red) incorporation. Proliferating  T cells can be seen both within  the IgD− germinal center (G)  and the surrounding IgD+ follicular mantle (FM). b–d (×160) are  serial sections from a draining  node 22 d after infection with  MMTV(SW) stained for IgD  (brown), BrdU (red) and blue  staining which shows PNA in b,  Vβ6 in c, and CD3 in d, respectively. Almost all the T cells  within the PNA+ germinal center (G) and around 10% of the T  cells in the T zone (T) express  Vβ6. Very few follicular Vβ6 T  cells are BrdU+; this applied to T  cells in follicles at all stages of the  response to MMTV(SW).
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Figure 7: Photomicrographs of stained sections to show germinal centers formed during responses to NP-CGG in a and MMTV(SW) in b–d within the draining LN. a (×250) shows a LN taken 8 d after immunization with NP-CGG stained for IgD (brown), CD3 (blue) and BrdU (red) incorporation. Proliferating T cells can be seen both within the IgD− germinal center (G) and the surrounding IgD+ follicular mantle (FM). b–d (×160) are serial sections from a draining node 22 d after infection with MMTV(SW) stained for IgD (brown), BrdU (red) and blue staining which shows PNA in b, Vβ6 in c, and CD3 in d, respectively. Almost all the T cells within the PNA+ germinal center (G) and around 10% of the T cells in the T zone (T) express Vβ6. Very few follicular Vβ6 T cells are BrdU+; this applied to T cells in follicles at all stages of the response to MMTV(SW).

Mentions: BALB/c mice were injected into both hind footpads with milk-purified infectious MMTV(SW) or alum-precipitated NP-CGG with killed B. pertussis microorganisms. The specific serum antibody titers of these immunized mice were measured and the immune responses in the draining popliteal LN were compared. To assess the proliferative response, mice were given a pulse of BrdU i.p. 2.5 h before death to identify and localize cells that had been in S phase of the cell cycle over this period. One draining popliteal LN was used to quantify cellular subsets by flow cytometry; the contralateral draining LN was used to colocalize these subsets by immunohistology. With both methods, cells were stained for cell differentiation and proliferation markers between day 0 and day 30 after antigen challenge. The antibody responses are shown in Fig. 1, while the flow cytometry data are shown in Figs. 2 and 4 and the histological analyses in Figs. 3, 5, 6, 7.


Viral superantigen drives extrafollicular and follicular B cell differentiation leading to virus-specific antibody production.

Luther SA, Gulbranson-Judge A, Acha-Orbea H, MacLennan IC - J. Exp. Med. (1997)

Photomicrographs  of stained sections to show germinal centers formed during responses to NP-CGG in a and  MMTV(SW) in b–d within the  draining LN. a (×250) shows a  LN taken 8 d after immunization  with NP-CGG stained for IgD  (brown), CD3 (blue) and BrdU  (red) incorporation. Proliferating  T cells can be seen both within  the IgD− germinal center (G)  and the surrounding IgD+ follicular mantle (FM). b–d (×160) are  serial sections from a draining  node 22 d after infection with  MMTV(SW) stained for IgD  (brown), BrdU (red) and blue  staining which shows PNA in b,  Vβ6 in c, and CD3 in d, respectively. Almost all the T cells  within the PNA+ germinal center (G) and around 10% of the T  cells in the T zone (T) express  Vβ6. Very few follicular Vβ6 T  cells are BrdU+; this applied to T  cells in follicles at all stages of the  response to MMTV(SW).
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Figure 7: Photomicrographs of stained sections to show germinal centers formed during responses to NP-CGG in a and MMTV(SW) in b–d within the draining LN. a (×250) shows a LN taken 8 d after immunization with NP-CGG stained for IgD (brown), CD3 (blue) and BrdU (red) incorporation. Proliferating T cells can be seen both within the IgD− germinal center (G) and the surrounding IgD+ follicular mantle (FM). b–d (×160) are serial sections from a draining node 22 d after infection with MMTV(SW) stained for IgD (brown), BrdU (red) and blue staining which shows PNA in b, Vβ6 in c, and CD3 in d, respectively. Almost all the T cells within the PNA+ germinal center (G) and around 10% of the T cells in the T zone (T) express Vβ6. Very few follicular Vβ6 T cells are BrdU+; this applied to T cells in follicles at all stages of the response to MMTV(SW).
Mentions: BALB/c mice were injected into both hind footpads with milk-purified infectious MMTV(SW) or alum-precipitated NP-CGG with killed B. pertussis microorganisms. The specific serum antibody titers of these immunized mice were measured and the immune responses in the draining popliteal LN were compared. To assess the proliferative response, mice were given a pulse of BrdU i.p. 2.5 h before death to identify and localize cells that had been in S phase of the cell cycle over this period. One draining popliteal LN was used to quantify cellular subsets by flow cytometry; the contralateral draining LN was used to colocalize these subsets by immunohistology. With both methods, cells were stained for cell differentiation and proliferation markers between day 0 and day 30 after antigen challenge. The antibody responses are shown in Fig. 1, while the flow cytometry data are shown in Figs. 2 and 4 and the histological analyses in Figs. 3, 5, 6, 7.

Bottom Line: The response to MMTV(SW) in draining lymph nodes was compared with the response to haptenated chicken gamma globulin (NP-CGG) using flow cytometry and immunohistology.Germinal centers develop in both responses, but those induced by MMTV(SW) appear later and are smaller.Most T cells activated in the T zone and germinal centers in the MMTV(SW) response are superantigen specific and these persist for weeks in lymph nodes draining the site MMTV(SW) injection: this contrasts with the selective loss of superantigen-specific T cells from other secondary lymphoid tissues.

View Article: PubMed Central - PubMed

Affiliation: Ludwig Institute for Cancer Research, University of Lansanne, Epalinges.

ABSTRACT
Mouse mammary tumor virus (MMTV[SW]) encodes a superantigen expressed by infected B cells. It evokes an antibody response specific for viral envelope protein, indicating selective activation of antigen-specific B cells. The response to MMTV(SW) in draining lymph nodes was compared with the response to haptenated chicken gamma globulin (NP-CGG) using flow cytometry and immunohistology. T cell priming occurs in both responses, with T cells proliferating in association with interdigitating dendritic cells in the T zone. T cell proliferation continues in the presence of B cells in the outer T zone, and B blasts then undergo exponential growth and differentiation into plasma cells in the medullary cords. Germinal centers develop in both responses, but those induced by MMTV(SW) appear later and are smaller. Most T cells activated in the T zone and germinal centers in the MMTV(SW) response are superantigen specific and these persist for weeks in lymph nodes draining the site MMTV(SW) injection: this contrasts with the selective loss of superantigen-specific T cells from other secondary lymphoid tissues. The results indicate that this viral superantigen, when expressed by professional antigen-presenting cells, drives extrafollicular and follicular B cell differentiation leading to virus-specific antibody production.

Show MeSH
Related in: MedlinePlus