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International Immunology Advance Access published online on August 23, 2004
International Immunology, doi:10.1093/intimm/dxh142
© 2004 by The Japanese Society for Immunology
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Received March 24, 2004
Accepted July 12, 2004

Article

Marginal zone B cells transport and deposit IgM-containing immune complexes onto follicular dendritic cells

Andrew R. Ferguson 1, Michele E. Youd 1, Ronald B. Corley 1*

1 Department of Microbiology, Boston University School of Medicine, Boston, MA 02118, USA

* To whom correspondence should be addressed. E-mail: rbcorley{at}bu.edu.


  Abstract

Secreted IgM and complement are important mediators in the optimal initiation of primary T-dependent humoral immune responses. Secreted IgM serves as a natural adjuvant by enhancing the immunogenicity of protein antigens, perhaps as a result of IgM's ability to facilitate antigen deposition onto follicular dendritic cells (FDCs) and promote rapid germinal center (GC) formation. To understand how IgM enhances adaptive immune responses, we investigated the mechanism by which IgM-containing immune complexes (IgM-IC) are transported to FDCs as a first step in GC formation. We demonstrate that IgM-IC localize first to the splenic marginal zone (MZ) where the IgM-IC bind MZ B cells in a complement and complement receptor (CR1/2) dependent process. MZ B cells then transport the IgM-IC into the follicle for deposition onto FDCs. Mice with reduced numbers of MZ B cells trap IgM-IC on FDC less efficiently, whereas mice with reduced numbers of follicular B cells trap IgM-IC normally. The functional elimination of MZ B cells abrogates the ability of FDCs to trap IgM-IC. Transfer of B cells with associated IgM-IC into naive mice results in deposition of IgM-IC onto FDC by MZ B cells. The results demonstrate an IgM and complement-dependent role for MZ B cells in the fate of antigen early in the initial phases of T-dependent immune responses. The data also establish an important role for CR1/2 on MZ B cells in the efficient binding and transport of IgM-IC to FDCs, which we suggest is an important first step in initiating adaptive immune responses.

Keywords: antigen transport; CD19; complement; complement receptors; germinal center.
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