Author(s)

Jun Tanaka, Kumiko Hirano, Yuzuru Sakamoto, Akiko Sugahara-Tobinai, Shota Endo, Yumi Ito-Matsuoka, Atsushi Nakano, Masanori Inui, Lars Nitschke, Toshiyuki Takai

Department of Experimental Immunology, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan.
Department of Genetics, University of Erlangen, Erlangen, Germany.
Osaka Research Laboratory, Benesis Corporation, Osaka, Japan.

A therapeutic preparation of polyclonal human IgG, i.e., intravenous immunoglobulin (IVIg), has been employed to treat several inflammatory and autoimmune disorders. B cells are supposed to be a target of IVIg, but the molecular mechanism is elusive because of the lack of a suitable experimental system. To gain an insight into the beneficial effect of IVIg on B cells, we first established an experimental setting in which IVIg modulates a murine B cell function in vitro, and then aimed at identifying the mechanistic features at the molecular level. Here we show that IVIg down-regulates IL-10 production by CpG-activated B cells in vitro. The responsible component of IVIg was identified as the F(ab’)₂ portion, whose polyclonality is mandatory for the suppressive effect. IVIg, bound to the surface of activated B cells, was found to be co-localized with intracellular SHP-1 on confocal laser microscopy, suggesting that B cell-surface immunoreceptor tyrosine-based inhibitory motif-harboring receptors that recruit SHP-1 are target molecules for IVIg in our experimental setting. Overall, we postulate a scenario in which IVIg attenuates B cells by suppressing IL-10 production, a B cell growth factor, and thus down-regulates the production of pathogenic antibodies.

F(ab’)2 Fragment; Immune Inhibition; ITIM Receptors; Polyclonal IgG; SHP-1

Tanaka, J. , Hirano, K. , Sakamoto, Y. , Sugahara-Tobinai, A. , Endo, S. , Ito-Matsuoka, Y. , Nakano, A. , Inui, M. , Nitschke, L. and Takai, T. (2012) Intravenous immunoglobulin suppresses IL-10 production by activated B cells in vitro. Open Journal of Immunology, 2, 149-160. doi: 10.4236/oji.2012.24019.