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Antibodies 2014, 3(2), 192-204; doi:10.3390/antib3020192
Review

Role of B Cells in Breaking and Maintaining Tolerance to Clotting Factor VIII in Congenital and Acquired Hemophilia A

1, 2 and 1,2,*
1 Department of Pathology and Laboratory Medicine, Medical School, University of Texas Health Science Center at Houston, TX 77030, USA 2 Program in Molecular Pathology, Graduate School of Biomedical Sciences, University of Texas Health Science Center at Houston, TX 77030, USA
* Author to whom correspondence should be addressed.
Received: 29 October 2013 / Revised: 1 March 2014 / Accepted: 24 March 2014 / Published: 8 April 2014
(This article belongs to the Special Issue B Cells and Immunological Tolerance)
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Abstract

Immune responses directed against clotting factor FVIII (FVIII) seriously complicate treatments for patients with hemophilia A. This response can manifest in congenital hemophilia A patients who generate inhibitor antibodies that bind and inactivate “transplanted” replacement FVIII, as well as in acquired hemophiliacs, whose immune systems have lost tolerance to self-FVIII. Regardless of the mechanism by which production of anti-FVIII inhibitor antibody is triggered, the maintenance of this deleterious response in both congenital and acquired hemophiliacs likely relies upon FVIII specific memory B cells. In this review, the similarities and differences in the kinetics, specificities, and subclasses of antibodies produced in response to allo- and auto-FVIII is outlined. A brief description of the immune cell interactions that contribute to maintenance of antibody response, focusing on development of memory B cells and/or long lived plasma cells is also presented. As current treatments for inhibitor antibodies are not successful in all patients, a better understanding of the functions and persistence of memory B cells specific for FVIII is required. Herein, both clinical and experimental data regarding the effects of immune tolerance induction on memory B cell subpopulations is discussed. Finally, the outcomes of B cell-specific depletion via rituximab in hemophilia and other autoimmune diseases are discussed to highlight insights into the subpopulations of memory B cells that contribute to the development and maintenance of successful tolerance to FVIII.
Keywords: hemophilia; autoimmunity; FVIII; B cells hemophilia; autoimmunity; FVIII; B cells
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

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Actor, A.M.; Holley, C.K.; Csencsits-Smith, K. Role of B Cells in Breaking and Maintaining Tolerance to Clotting Factor VIII in Congenital and Acquired Hemophilia A. Antibodies 2014, 3, 192-204.

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