# REGULATION OF IGA RESPONSES IN LPSN AND LPSD MICE

> **NIH NIH R01** · UNIVERSITY OF ALABAMA AT BIRMINGHAM · 1989 · $121,644

## Abstract

The overall objective of this research proposal is to provide direct
evidence that bacterial lipopolysaccharide (LPS) affects both T and B
lymphocytes in gut-associated lymph-oreticular tissue (GALT).  It will be
shown that the interaction of LPS with GALT T cells results in a
subpopulation which can be induced by thymic dependent antigen to become
mature T suppresor (Ts) cells, while interaction with GALT B cells results
in the induction of a mature population which includes precursor cells for
IgA responses.  For these proposed studies, we will employ unique mouse
models including:  1) LPS responsive C3H/HeN and syngeneic LPS
nonresponsive C3H/HeJ mice; 2) germfree (GF, LPS-free) C3H/HeN and C3H/HeJ
mice and their conventional (Conv.) counterparts; and 3) X-linked immune
deficient (xid) mice with either CBA/N, C3H/HeJ or C3H/HeN backgrounds.
GALT T cell subpopulations from C3H/HeN and C3H/HeJ mice will be compared
for numbers and intensity of Thy- 1.2+, Lyt-1+, and Lyt-2+ cells by FACS
analysis.  In another series, GALT T cells from LPS responsive mice (and
C3H/HeJ as controls) will be treated with LPS in vitro and assessed for
phenotypic conversion.  Phenotypic conversion will also be investigated in
vivo after chronic oral administration of LPS to GF C3H/HeN mice and
assessment of antigen inducible Ts cells in vivo and in vitro.  LPS effects
on GALT B cells, with emphasis on IgA precursors, will be determined by
comparison of GF and Conv B cell subpopulations for maturation markers
including surface immunoglobulin (sIg), I-A, complement receptor (CR), and
Lyb differentiation antigens.  GF mice, which have been shown to exhibit
immature B cell subpopulations, will be induced to maturation by chronic
gastrointestinal exposure to LPS, and LPS induced B cell maturation in
these mice will be assessed by induction of IgA responses.  The
relationship between LPS sensitivity and the ability to induce oral
tolerance will be studied at both the T and B cell level in GALT using
C3H/HeN and C3H/HeJ xid and normal mice.  By using offspring from
appropriate matings, T helper (Th) cells for IgA responses will be induced
in the presence of either immature or normal B cell subpopulations.
Furthermore, the induction of B cell tolerance in the presence of either Th
or Ts cell populations will be studied.

## Key facts

- **NIH application ID:** 3129029
- **Project number:** 2R01AI019674-05A2
- **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:** 1989
- **Award amount:** $121,644
- **Award type:** 2
- **Project period:** 1983-09-01 → 1991-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3129029

## Citation

> US National Institutes of Health, RePORTER application 3129029, REGULATION OF IGA RESPONSES IN LPSN AND LPSD MICE (2R01AI019674-05A2). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3129029. Licensed CC0.

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