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Exploitation of host signaling pathways by B cell superantigens--potential strategies for developing targeted therapies in systemic autoimmunity.

Abstract
Some infectious agents produce molecules capable of interacting specifically with the immunoglobulin heavy- or light-chain variable regions, independently of the conventional-binding site. They are referred to as B cell superantigens (SAgs) and include protein A of Staphylococcus aureus (S. aureus), gp120 of HIV-1, and protein L of Peptostreptococcus magnus (P. magnus). In contrast to conventional antigens, B cell superantigens interact with conserved framework regions of immunoglobulins and can target a large proportion of B cells. In experimental models, they have been demonstrated to deplete B cell subsets responsible for innate functions, namely B-1a and marginal zone (MZ) B cells. As a result, the interactions of these superantigens with host cells impair the humoral immune response. In addition to providing clues toward understanding host-pathogen interactions and microbial pathogenesis, B cell superantigens represent potential therapeutic agents that could be used to specifically modulate expansion of B cell subsets in diseased subjects. In systemic autoimmune diseases, for example, there is activation and expansion of B cells that secrete pathogenic autoantibodies. Their depletion results in clinical improvement in both experimental animals and patients. Currently, attempts are being made to specifically deplete pathogenic autoantibody-producing B cells. Since B-1a and MZ B cells have been found to be expanded in autoimmune disorders, B cell superantigens, used alone or in combination with other biological agents, may have beneficial effects in autoimmune disease management.
AuthorsMoncef Zouali
JournalAnnals of the New York Academy of Sciences (Ann N Y Acad Sci) Vol. 1095 Pg. 342-54 (Jan 2007) ISSN: 0077-8923 [Print] United States
PMID17404047 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)
Chemical References
  • Superantigens
Topics
  • Animals
  • Autoimmune Diseases (immunology, microbiology, therapy, virology)
  • B-Lymphocytes (immunology, microbiology, virology)
  • Humans
  • Signal Transduction (immunology)
  • Superantigens (immunology)

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