| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
* Department of Microbiology and Immunology, and
Department of Anatomy and Neurobiology and The Immunology Group, Virginia Commonwealth University, Richmond, VA 23298
Follicular dendritic cells (FDCs) periodically arrange membrane-bound immune complexes (ICs) of T-dependent Ags 200–500Å apart, and in addition to Ag, they provide B cells with costimulatory signals. This prompted the hypothesis that Ag in FDC-ICs can simultaneously cross-link multiple BCRs and induce T cell-independent (TI) B cell activation. TI responses are characterized by rapid IgM production. OVA-IC-bearing FDCs induced OVA-specific IgM in anti-Thy-1-pretreated nude mice and by purified murine and human B cells in vitro within just 48 h. Moreover, nude mice immunized with OVA-ICs exhibited well-developed GL-7+ germinal centers with IC-retaining FDC-reticula and Blimp-1+ plasmablasts within 48 h. In contrast, FDCs with unbound-OVA, which would have free access to BCRs, induced no germinal centers, plasmablasts, or IgM. Engagement of BCRs with rat-anti-mouse IgD (clone 11–26) does not activate B cells even when cross-linked. However, B cells were activated when anti-IgD-ICs, formed with Fc-specific rabbit anti-rat IgG, were loaded on FDCs. B cell activation was indicated by high phosphotyrosine levels in caps and patches, expression of GL-7 and Blimp-1, and B cell proliferation within 48 h after stimulation with IC-bearing FDCs. Moreover, anti-IgD-IC-loaded FDCs induced strong polyclonal IgM responses within 48 h. Blockade of FDC-Fc
RIIB inhibited the ability of FDC-ICs to induce T-independent IgM responses. Similarly, neutralizing FDC-C4BP or -BAFF, to minimize these FDC-costimulatory signals, also inhibited this FDC-dependent IgM response. This is the first report of FDC-dependent but TI responses to T cell-dependent Ags.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by National Institutes of Health (NIH) (AI-17142) and VaxDesign grants (to J.G.T.). The confocal microscopy was performed at the Virginia Commonwealth University, Department of Anatomy and Neurobiology Microscopy Facility, supported, in part, with funding from NIH, National Institute of Neurological Disorders and Stroke Center Core Grant 5P30NS047463 to the Department of Anatomy and Neurobiology.
2 This document was cleared for public release (distribution unlimited) by the Defense Advanced Research Projects Agency.
3 M.E.M.E. and R.M.E. contributed equally to this work and therefore share the first authorship.
4 Address correspondence and reprint requests to Dr. John G. Tew, Virginia Commonwealth University, Department of Microbiology and Immunology, P.O. Box 980678, Richmond, VA 23298-0678. E-mail address: tew{at}vcu.edu
5 Abbreviations used in this paper: TD, T cell dependent; ARR, Ag-retaining reticula; BAFF, B cell-activating factor belonging to the TNF family; Blimp-1, B lymphocyte-induced maturation protein-1; C4BP, C4b-binding protein; FDC, follicular dendritic cell; GC, germinal center; IC, immune complex; LN, lymph node; MFI, mean fluorescence intensity; MHC, MHC class II; NIP, 4-hydroxy-3-iodo-5-nitrophenylacetyl; TI, T cell independent; TNP, trinitrophenol.
Related articles in The JI:
This article has been cited by other articles:
|
|
 |
|
  K. Hannestad and H. Scott The MHC Haplotype H2b Converts Two Pure Nonlupus Mouse Strains to Producers of Antinuclear Antibodies J. Immunol., September 1, 2009; 183(5): 3542 - 3550. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
