Extrafollicular Plasmablast B Cells Play a Key Role in Carrying Retroviral Infection to Peripheral Organs

Finke, Daniela; Baribaud, Frédéric; Diggelmann, Heidi; Acha‐Orbea, Hans

doi:10.4049/jimmunol.166.10.6266

Cited by 35 publications

(39 citation statements)

References 69 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Several studies have clearly demonstrated that MMTV is transported to the mammary gland by lymphocytes and that infected B and T cells can release MMTV particles (6)(7)(8)(9). Because removal of the draining LN after virus infection abolished the neutralizing Ab responses, we were able to address the viral spread to lymphoid and nonlymphoid compartments in the absence of neutralizing Abs.…”

Section: Viral Infection and Tumor Development In The Absence Of Neutmentioning

confidence: 76%

“…To study whether the chronic GC response in the draining LN plays a role in maintaining virus-neutralizing Ab responses and͞or viral infection we removed the draining popliteal LN after installation of a systemic infection. Day 4 after footpad injection is the peak of the extrafollicular B cell response when infected plasmablast B cells exit the draining LN and home to peripheral tissues (9). GC are initiated by days 9-10, and by day 23 a chronic GC response in the draining LN is established.…”

Section: Resultsmentioning

confidence: 99%

“…To semiquantify the number of MMTV(SW)-infected cells, DNA from BALB.D2 mice containing two copies of the endogenous provirus Mtv-7 per cell was amplified from 10-fold dilutions of DNA starting with 50 ng of DNA mixed with 450 ng of DNA of BALB͞c mice, keeping the total DNA concentration constant. The PCR product was detected by liquid hybridization by using the end-labeled radioactive oligonucleotide 5Ј-CAA GGA GGT CTA GCT CTG GCG-3Ј as described (9). The annealing reaction was performed with one cycle consisting of 5 min at 98°C and one cycle consisting of 15 min at 55°C.…”

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

The role of neutralizing antibodies for mouse mammary tumor virus transmission and mammary cancer development

Finke

Luther²,

Acha‐Orbea³

2002

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

View full text Add to dashboard Cite

Mouse mammary tumor virus (MMTV) infection establishes chronic germinal centers and a lifelong neutralizing Ab response. We show that removal of the draining lymph node after establishment of the germinal center reaction led to complete loss of neutralizing Abs despite comparable infection levels in peripheral lymphocytes. Importantly, in the absence of neutralization, only the exocrine organs mammary gland, salivary gland, pancreas, and skin showed strikingly increased infection, resulting in accelerated mammary tumor development. Induction of stronger neutralization did not influence chronic infection levels of peripheral lymphoid organs but strongly inhibited mammary gland infection and virus transmission to the next generation. Taken together, we provide evidence that a tight equilibrium in virus neutralization allows limited infection of exocrine organs and controls cancer development in susceptible mouse strains. These experiments show that a strong neutralizing Ab response induced after infection is not able to control lymphoid MMTV infection. Strong neutralization, however, is capable of blocking amplification of mammary gland infection, tumor development, and virus transmission to the next generation. The results also indicate a role of neutralization in natural resistance to MMTV infection.

show abstract

Section: Viral Infection and Tumor Development In The Absence Of Neutmentioning

confidence: 76%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

The role of neutralizing antibodies for mouse mammary tumor virus transmission and mammary cancer development

Finke

Luther²,

Acha‐Orbea³

2002

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

View full text Add to dashboard Cite

show abstract

“…Important knowledge has been obtained by utilization of the adult mouse infection model (Ardavin et al, 1999). By using that model, it has been shown that infected B cells differentiate into IgG-secreting plasma cells (Held et al, 1993) and that B220 low cells are able to carry the virus to other organs, including mammary glands (Finke et al, 2001). However, it is unlikely that the same events take place during MMTV natural infection because the virus enters through the GALT, a mucosal tissue where B cells are very prone to switching to IgA (Butcher et al, 1982;Weisz-Carrington et al, 1977).…”

Section: Mmtv Infection Causes Increases In Pp Igamentioning

confidence: 99%

Increases in IgA+ B cells in Peyer's patches during milk-borne mouse mammary tumor virus infection are influenced by Toll-like receptor 4 and are completely dependent on the superantigen response

Cabrera

Vercelli

Burzyn

et al. 2010

Journal of General Virology

View full text Add to dashboard Cite

Mouse mammary tumor virus (MMTV) is a milk-borne betaretrovirus that has developed strategies to exploit and subvert the host immune system. Although mammary glands are the final target of infection, Peyer's patches (PP) are the entry site of the virus. Herein, we show that the infection induces increases in the number of PP IgA + B cells and higher expression of the a circular transcript, which is a specific marker of the switch to IgA. In addition, IgA + B-cell increases correlated with higher levels of cytokines related to IgA class switching, such as interleukin (IL)-5 and IL-6. Of interest, the increases in IgA + B cells were lower in Toll-like receptor 4-deficient mice and were completely dependent on the presence of superantigen-reactive T cells. Our results point to a novel mechanism involved in MMTV infection and suggest that IgA + B cells may play an important role in carrying the virus to the mammary glands.

show abstract

“…DNA extracted from cells of different origins was analyzed by PCR as described previously (16). In brief, 50 ng of DNA isolated from LNs, spleens, and mammary glands was analyzed by PCR with specific primers for exogenous MMTV SW. Primers for Mtv-6, -8, and -9 were used as positive controls.…”

Section: Methodsmentioning

confidence: 99%

Passive Immunization with Neutralizing Antibodies Interrupts the Mouse Mammary Tumor Virus Life Cycle

Mpandi

Otten

Lavanchy

et al. 2003

J Virol

View full text Add to dashboard Cite

Mouse mammary tumor virus (MMTV) infects the host via mucosal surfaces and exploits the host immune system for systemic spread and chronic infection. We have tested a neutralizing rat monoclonal antibody specific for the retroviral envelope glycoprotein gp52 for its efficiency in preventing acute and chronic mucosal and systemic infection. The antibody completely inhibits the superantigen response and chronic viral infection following systemic or nasal infection. Surprisingly however, the antibody only partially inhibits the early infection of antigen-presenting cells in the draining lymph node. Despite this initially inefficient protection from infection, superantigen-specific B-and T-cell responses and systemic viral spread are abolished, leading to complete clearance of the retroviral infection and hence interruption of the viral life cycle. In conclusion, systemic neutralizing monoclonal antibodies can provide an efficient protection against chronic retroviral amplification and persistence.The retrovirus mouse mammary tumor virus (MMTV) is transmitted from infected mothers to offspring via milk during the first 2 weeks after birth. MMTV targets three major cell types for infection: dendritic cells (DC) (33, 42) and B lymphocytes (9, 22) early in infection and epithelial cells of exocrine secretory organs later on (for a review see reference 31). Once MMTV has crossed the mucosa it infects DC and B cells in the Peyer's patches (PP) before spreading to peripheral organs (27). Chronic infection of the mammary gland leads to viral transmission via milk and to mammary tumor development after retroviral insertion next to proto-oncogenes (34). Adult mice can be chronically infected by subcutaneous (s.c.) injection (23) or by nasal administration of the virus (44). After entry into the cell, viral RNA is reverse transcribed and the resulting viral DNA is integrated into the genome in target DC and B cells. This leads to expression of a viral superantigen (SAg) at the cell surface (22). Oral, s.c., and nasal routes of infection proceed with similar kinetics, which are dominated by efficient priming of a SAg T-cell response via an interaction between infected B cells and DC-primed SAg-reactive cognate T cells. SAg-activated T cells are slowly deleted from the peripheral T-cell repertoire. This deletion represents one of the most sensitive readouts for chronic infection and systemic spread of MMTV. While the virus persists in all lymphoid and nonlymphoid organs, MMTV establishes a chronic immune response with germinal centers, persisting antigen (Ag), and virus-specific B and T cells only in the draining lymph node (LN). This leads to a weak life-long neutralizing antibody (Ab) response against the viral envelope (Env) protein gp52 (32). Although in susceptible mice this chronic Ab response is unable to clear the virus infection, resistant mouse strains such as I/LnJ have evolved a strong neutralizing Ab response that controls chronic infection and prevents infection of the progeny (39). This is in agreement with the r...

show abstract

Extrafollicular Plasmablast B Cells Play a Key Role in Carrying Retroviral Infection to Peripheral Organs

Cited by 35 publications

References 69 publications

The role of neutralizing antibodies for mouse mammary tumor virus transmission and mammary cancer development

The role of neutralizing antibodies for mouse mammary tumor virus transmission and mammary cancer development

Increases in IgA+ B cells in Peyer's patches during milk-borne mouse mammary tumor virus infection are influenced by Toll-like receptor 4 and are completely dependent on the superantigen response

Passive Immunization with Neutralizing Antibodies Interrupts the Mouse Mammary Tumor Virus Life Cycle

Contact Info

Product

Resources

About