# CELLULAR AND MOLECULAR BASIS FOR THE IGA RESPONSE

> **NIH NIH R01** · UNIVERSITY OF ALABAMA AT BIRMINGHAM · 1990 · $187,564

## Abstract

The broad objective of this research is to elucidate the molecular events
involved in regulation of lgA responses at mucosal sites.  Our studies
have shown that higher mammals possess a common mucosal immune system in
which ingested antigens sensitize B and T cells in gut-associated
lymphoreticular tissue (GALT), e.g., the Peyer's patches (PP).  T helper
(Th) cells regulate the inductive phase in PP, and it is thought that Th
and lgA-committed B cells home to diverse mucosal effector regions such as
the lamina propria of the gastrointestinal (Gi) tract for lgA synthesis.
However, the precise mechanisms involved in regulation of this response
remain unknown.  Our past work has shown that PP dendritic cell (DC)-T
cell mixtures significantly enhance lgA synthesis.  Further,
antigenspecific PP Th cell clones were shown to selectively support lgA
responses, clearly indicating that GALT is an lgA inductive site.  Recent
studies have shown that recombinant interleukins, especially lL-5 and lL-
6, support enhance lgA synthesis in PP B cell cultures.  The lL-5- and lL-
6-induced  increase in lgA synthesis was confined to nongerminal center,
surface lgA-positive (sigA+) B cells.  This subset also repopulates lamina
propria regions upon adoptive transfer to SCID mice which suggests that
mature sigA+ B cells are sensitive to cytokines when they exit GALT.  In
this new renewal application we will define the T cell and cytokine
requirements for sigM+ B cell switches to sigA+ in PP germinal centers by
using highly purified B cell subsets and virus-transformed B cell lines
from GALT.  We will continue our studies to define the cytokine events
involved in B cell activation, division and terminal differentiation to
lgA synthesis, with special emphasis on cloned PP Th2 cells and lL-5 and
lL-6.  We will extensively use the single-cell ELISPOT assay to determine
the relative frequencies of Th1 (lL-2 and lFNgamma) and Th2 (lL-5 and  lL-
6) cells in GALT and lamina propria regions, for their roles in production
of switch cytokines (TGFbeta) and cytokines inducing terminal
differentiation to lgA synthesis (lL-5 and lL-6).  We will extensively use
two animals models to insure that the in vitro effects of cytokines
represent the actual events that occur in vivo.  Mice chronically depleted
of CD4+ Th cells by immunotoxin-     conjugated anti-CD4 mAbs which
inactivate ribosomes and protein synthesis in CD4+ T cells will be used to
show that the development of lgA plasma cells in       effector mucosal
sites is T cell dependent, while SCID mice will be used as adoptive hosts
for cloned PP Th cells and slgA+ B cell subsets that respond to
interleukins and that repopulate mucosal sites.  We will study the antigen
presenting cell functions of PP slgA+ and slgA- B cells and DC for
effective induction of lgA responses.  Finally, we will determine the
mechanism(s) involved in PP DC-Th cell induction of pre-B  B cell
maturation in GALT, including a possible role for lL-7.

## Key facts

- **NIH application ID:** 3128353
- **Project number:** 2R01AI018958-09
- **Recipient organization:** UNIVERSITY OF ALABAMA AT BIRMINGHAM
- **SAM.gov UEI:** YND4PLMC9AN7
- **Principal Investigator:** Jerry R McGhee
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1990
- **Award amount:** $187,564
- **Award type:** 2
- **Project period:** 1982-09-30 → 1994-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3128353

## Citation

> US National Institutes of Health, RePORTER application 3128353, CELLULAR AND MOLECULAR BASIS FOR THE IGA RESPONSE (2R01AI018958-09). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3128353. Licensed CC0.

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