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

Abstract

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.

Critical Review on Zeolite Clinoptilolite Safety and Medical Applications in vivo

“…Even though the exact mechanisms remain elusive, one may speculate that clinoptilolite silica or released silica acts as a superantigen that promotes the formation of IgA producing plasma cells, which is dependent on the presence of superantigen-reactive T cells. A similar superantigen effect was already observed in Peyer’s patches during milk-borne mouse mammary tumor virus infection ( Cabrera et al, 2010 ). To our knowledge, no negative effects on immune cells or tissue were documented in the scientific literature so far.…”

Antiproliferative activity and mode of action analysis of novel amino and amido substituted phenantrene and naphtho[2,1-b]thiophene derivatives

“…Even though the exact mechanisms remain elusive, one may speculate that clinoptilolite silica or released silica acts as a superantigen that promotes formation of IgA producing plasma cells, which is dependent on the presence of superantigenreactive T cells. A similar superantigen effect was already observed in Peyer's patches during milk-borne mouse mammary tumour virus infection [86]. We cannot however, rule out some other, unrecognized immunomodulatory effects of clinoptilolite due to a direct interaction with human microbiome as well (Figure 3 ).…”

Intestinal Immune System and Amplification of Mouse Mammary Tumor Virus

“…On the other hand, Th2 cells could produce IL-4 in order to induce B cell proliferation and class switching. IL-5 and IL-6 were also upregulated in these studies ( Mora and Von Andrian, 2008 ; Cabrera et al., 2010 ). Jude et al.…”

“…This activation process was likewise independent of MMTV expression ( Rassa et al., 2002 ; Burzyn et al., 2004 ). The positive correlation between TLR4 expression and B cell class switching also provided a lateral demonstration ( Cabrera et al., 2010 ). However, whether TLR4 is essential for MMTV-related activation or not and the exact significance of TLR4 in the infectious process of MMTV remain unclear.…”