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Prepublished online as a Blood First Edition Paper on December 12, 2002; DOI 10.1182/blood-2002-06-1684.
Submitted June 7, 2002
Accepted November 29, 2002
Intravenous immunoglobulins induce the in vitro differentiation of human B lymphocytes and the secretion of IgG
Marie Joelle de Grandmont, Claudia Racine, Annie Roy, Real Lemieux, and Sonia Neron*
Recherche et Developpement, Hema-Quebec, Sainte-Foy, Quebec, Canada; Biochimie et microbiologie, Universite Laval, Sainte-Foy, Quebec, Canada
Recherche et Developpement, Hema-Quebec, Sainte-Foy, Quebec, Canada
* Corresponding author; email: sneron{at}hema-quebec.qc.ca.
The therapeutic effects of intravenous immunoglobulins (IVIG) in several autoimmune diseases are characterized by a decrease in pathologic autoantibody levels. Although few direct evidences have been reported in humans, the large repertoire of natural IgG antibodies in IVIG is expected to be involved in the regulation of auto-reactive B lymphocytes. In normal adult mice, IVIG has been reported to modulate immature B cells as well as peripheral B lymphocytes through V-region connections. Studies with human serum also indicated that anti-idiotypic antibodies, present in IVIG preparations, could recognize both natural and pathologic autoantibodies. We have used an in vitro culture system to characterize the direct effect of IVIG on human B lymphocytes. This in vitro culture system involves CD40-activation of B lymphocytes by its ligand CD154 in presence of cytokines. In this system, addition of IVIG decreased by 50 to 80% the expansion of B lymphocytes. This reduced expansion was due to a decrease in the proliferation rate. In addition, a portion of B lymphocytes was differentiated into IgG-secreting cells in presence of IVIG and the secreted IgG were reactive with antigens such as nucleoprotamine, dsDNA, tetanus toxin,and human IgG F(ab')2 fragments. These observations indicate that IVIG can have direct effects on B lymphocytes and suggest that such IVIG regulation of B lymphocytes could be involved in the therapeutic effects of IVIG in autoimmune diseases.
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