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Prepublished online as a Blood First Edition Paper on December 12, 2002; DOI 10.1182/blood-2002-06-1684.
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Blood, 15 April 2003, Vol. 101, No. 8, pp. 3065-3073
IMMUNOBIOLOGY
Intravenous immunoglobulins induce the in vitro
differentiation of human B lymphocytes and the secretion of
IgG
Marie Joëlle de Grandmont,
Claudia Racine,
Annie Roy,
Réal Lemieux, and
Sonia Néron
From the Héma-Québec, Recherche et
Développement, Sainte-Foy, Québec, Canada; and the
Département de Biochimie et Microbiologie, Université
Laval, Québec, Canada.
The therapeutic effects of intravenous immunoglobulins (IVIGs) in
several autoimmune diseases are characterized by a decrease in
pathologic autoantibody levels. Although little direct evidence has
been reported in humans, the large repertoire of natural immunoglobulin G (IgG) antibodies in IVIGs is expected to be involved in the regulation of autoreactive B lymphocytes. In normal adult mice, IVIGs have 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 IVIGs on human B lymphocytes. This in vitro
culture system involves CD40 activation of B lymphocytes by its ligand
CD154 in the presence of cytokines. In this system, addition of
IVIGs 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 the presence of IVIGs and the secreted IgGs
were reactive with antigens such as nucleoprotamine, dsDNA, tetanus
toxin, and human IgG F(ab')2 fragments. These observations indicate that IVIGs can have direct effects on B lymphocytes and suggest that such IVIG regulation of B lymphocytes could be
involved in the therapeutic effects of IVIGs in autoimmune diseases.
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