Natural human polyreactive IgM induce apoptosis of lymphoid cell lines and human peripheral blood mononuclear cells

Varambally, Sooryanarayana; Bar‐Dayan, Yaron; Bayry, Jagadeesh; Lacroix‐Desmazes, Sébastien; Horn, Michael P.; Sorel, Marc; Bar‐Dayan, Yosefa; Ruberti, Giovina; Kazatchkine, Michel D.; Kaveri, Srini V.

doi:10.1093/intimm/dxh053

Cited by 37 publications

(32 citation statements)

References 64 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…75,76 Clinical and experimental data support a potential role of complement in the control of neoplastic cells. In cancer patients, endogenous complement activation has been demonstrated with subsequent deposition of complement components on tumor tissue.…”

Section: Mechanisms Of Cell Lysismentioning

confidence: 96%

Naturally Occurring Antibodies Directed Against Carbohydrate Tumor Antigens

Schwartz‐Albiez

2012

Advances in Experimental Medicine and Biology

View full text Add to dashboard Cite

Healthy persons carry within their pool of circulating antibodies immunoglobulins preferentially of IgM isotype, which are directed against a variety of tumor-associated antigens. In closer scrutiny of their nature, some of these antibodies could be defined as naturally occurring antibodies due to the germline configuration of the variable immunoglobulin region. The majority of these immunoglobulins recognize carbohydrate antigens which can be classified as oncofetal antigens. Many of these IgM antibodies present in the peripheral blood circulation can bind to tumor cells and of these a minor portion are also able to destroy tumor cells by several mechanisms, as for instance complement-mediated cytolysis or apoptosis. It was postulated that anti-carbohydrate antibodies are part of an anti-tumor immune response, while their presence in the peripheral blood of healthy donors is still waiting for a plausible explanation. It may be that recognition of defined epitopes, including carbohydrate sequences, by naturally occurring antibodies constitutes the humoral arm of an anti-tumor immune response as part of the often postulated tumor surveillance. The cytotoxic capacity of these antibodies inspired several research groups and pharmaceutical companies to design novel strategies of immunoglobulin-based anti-tumor immunotherapy.

show abstract

Section: Mechanisms Of Cell Lysismentioning

confidence: 96%

Naturally Occurring Antibodies Directed Against Carbohydrate Tumor Antigens

Schwartz‐Albiez

2012

Advances in Experimental Medicine and Biology

View full text Add to dashboard Cite

show abstract

“…The IgM-induced cell death involved classic features of apoptosis, such as nuclear fragmentation and activation of caspases (14). Soluble Fas molecules inhibited this natural autoantibody-induced apoptosis, suggesting that the Fas pathway is involved.…”

Section: Natural Autoantibodies As Protective Immunoglobulinsmentioning

confidence: 96%

Protective autoantibodies: Role in homeostasis, clinical importance, and therapeutic potential

Shoenfeld¹,

Toubi²

2005

Arthritis & Rheumatism

View full text Add to dashboard Cite

“…Nef. Recently, it has been reported that in preparation of the natural IgM fraction, antibodies reactive with Fas were shown to have the capacity to induce apoptosis of lymphoblastoid cells (19). On the other hand, 2G9 reacted with HIV-1-infected cells, in which Fas expression is downregulated indicating that it does not react with Fas.…”

Section: Discussionmentioning

confidence: 99%

Human IgM Monoclonal Antibodies Reactive with HIV‐1‐Infected Cells Generated Using a Trans‐Chromosome Mouse

Okada

Yin

Asai

et al. 2005

Microbiology and Immunology

View full text Add to dashboard Cite

The trans‐chromosome (TC) mouse that we used harbors human chromosomes 2, 14 and/or 22, and has undergone knock‐out of its endogeneous genes coding for μ‐ and κ‐chains of immunoglobulin. One of these TC mice was immunized with HIV‐1‐infected U937 cells, and spleen cells from the immunized animal were fused with the mouse myeloma cell line to generate hybridoma cells. We selected hybridomas that produce human IgM antibodies (Abs) reactive with HIV‐1‐infected MOLT4 cells but not with uninfected MOLT4 cells. Two hybridoma cell lines were established termed 9F11 and 2G9. Although 0.4 μg/ml of 9F11 was able to induce complement‐mediated cytolysis of the infected cells in the presence of fresh human serum, 2G9 could not. There was no difference between the two monoclonal Abs in the base sequences of cDNAs coding for the constant regions of μ‐ and κ‐chains. Therefore, we speculate that the ability to activate complement on homologous cell membranes might reflect the structural presentation of antigenic molecules, which could facilitate the binding of an IgM Ab to multiple binding sites resulting in escape from restriction by species‐specific inhibitors of complement such as DAF (CD55) and CD59. On the other hand, 2G9 induced apoptosis of HIV‐1‐infected cells, including latently infected OM10.1 cells, although the Ag for 2G9 remains to be identified. Since both of the Abs had reduced reactivity toward HIV‐1‐infected MOLT4 cells following cultivation in the presence of tunicamycin, the responsible antigens would involve a sugar moiety.

show abstract

Natural human polyreactive IgM induce apoptosis of lymphoid cell lines and human peripheral blood mononuclear cells

Cited by 37 publications

References 64 publications

Naturally Occurring Antibodies Directed Against Carbohydrate Tumor Antigens

Naturally Occurring Antibodies Directed Against Carbohydrate Tumor Antigens

Protective autoantibodies: Role in homeostasis, clinical importance, and therapeutic potential

Human IgM Monoclonal Antibodies Reactive with HIV‐1‐Infected Cells Generated Using a Trans‐Chromosome Mouse

Contact Info

Product

Resources

About