# ROLE OF FOLLICULAR ANTIGEN-BINDING DENDRITIC CELLS

> **NIH NIH R01** · VIRGINIA COMMONWEALTH UNIVERSITY · 1988 · $121,808

## Abstract

This proposal focuses on one of the most basic questions in immunology:
i.e., what happens to the immunogen during the induction of a secondary
response?  Immunogens encounter antibody in immune animals and are almost
instantaneously converted into immune complexes.  These complexes are
quickly trapped, endocytosed, and catabolized by macrophages.  Certain
antigen fragments may be expressed on macrophage membranes in a
conformation that is recognizable by T cells.  Our data indicates this
process occurs quickly and by 48 hours after immunization very little
antigen persists in or on these macrophages.  However, an alternative
antigen pathway exists which tends to preserve the immunogen.  Initially
the immune complexes are trapped on the surface of non-phagocytic cells
which transport these complexes to follicular dendritic cells (FDCs) deep
in the lymph node outer cortex.  Recently, we observed that after encounter
with immune complexes the dendrites of many FDCs appear "beaded".  These
beads represent antigen coated spherical structures we call microspheres
and these microspheres are released into the surrounding microenvironment.
We have documented that these antigen coated microspheres are endocytosed
by germinal center B cells and tingible body macrophages (TBMs) which
accumulate in the follicles.  We believe these cells are processing this
antigen for presentation to appropriate T cells.  This process continues
for at least 8 days.  We hypothesize that Ag in this alternative pathway
may help initiate the secondary response, and more importantly, we propose
that it serves to amplify the response and helps explain the induction of
the high levels of specific antibody associated with anamnestic responses.
In addition we propose that it serves to maintain and regulate serum
antibody levels by initiating a new round of antibody production each time
the level of specific antibody in the animal declines.  Major tenants of
this hypothesis are that FDCs present Ag to B cells and that germinal
center B cells or TBMs present Ag to T cells.  The major thrust of the
proposed work is to determine if FDCs can present Ag to B cells and if
germinal center B cells and TBMs can present Ag to T cells.  Finally we
propose to examine how Ab feedback regulation interacts in this process.

## Key facts

- **NIH application ID:** 3126992
- **Project number:** 5R01AI017142-09
- **Recipient organization:** VIRGINIA COMMONWEALTH UNIVERSITY
- **SAM.gov UEI:** MLQFL4JSSAA9
- **Principal Investigator:** John G Tew
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1988
- **Award amount:** $121,808
- **Award type:** 5
- **Project period:** 1980-09-01 → 1991-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3126992

## Citation

> US National Institutes of Health, RePORTER application 3126992, ROLE OF FOLLICULAR ANTIGEN-BINDING DENDRITIC CELLS (5R01AI017142-09). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3126992. Licensed CC0.

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