# MECHANISMS OF AUTOREACTIVITY IN SLE

> **NIH NIH R01** · UNIV OF NORTH CAROLINA CHAPEL HILL · 1993 · $212,039

## Abstract

The MRL/Mp-Ipr/lpr (MRL/lpr) mouse strain spontaneously develops a
systemic autoimmune disease which has striking resemblance to human SLE
in its serological specificities and immunopathology.  The genetic
control of the disease in these mice is determined by the autosomal
recessive lpr gene as well as by the background genes of the MRL strain.
The current application will continue studies of the fundamental
mechanisms involved in autoantibody production in the MRL/lpr mouse.  It
will target particularly the anti-Sm specificity, but will also study
other autoantibodies and immunopathology.  The proposed experiments will
investigate the (molecular) genetic , cellular, stochastic, and
environmental effects on disease expression.  The grant is divided into
five hypothesis-based Specific Aims.  1)  Hypothesis:  A large but
restricted subset of immunoglobulin genes is utilized for the spontaneous
anti-Sm response.  The ongoing investigation of the V/H and V/L genes
from anti-Sm hybridomas will be continued to understand the repeated use
of certain V/H genes and the role of somatic mutation.  2) Hypothesis:
The bimodal distribution of the anti-Sm response in MRL/lpr mice is due
to the random generation of specific T-helper cells.  Thymectomized,
irradiated, bone-marrow-reconstituted chimeras will be utilized to
determine the specificity of T cells for anti-Sm antibody formation.  3)
Hypothesis:  The critical influence of the MRL background genes on the
generation of anti-Sm positivity is expressed at T-cell (or,
alternatively, at the B-cell) level.  Mixed chimeras of anti-Sm+ and
anti-Sm-lpr mice will be used to elucidate the cellular level of control
of anti-Sm formation by the MRL background genes.  4)  Hypothesis:
Environmental effects on the development of the immune system are
irrelevant to the production of systemic autoimmunity in MRL mice.  Germ-
free and antigen-free MRL/lpr mice will be investigated for their
autoimmune syndrome.  5)  Hypothesis:  The two murine class II loci (I-A
and I-E) are not utilized equivalently in the generation of the anti-Sm
response.  The possibility that T-B collaboration restricted to
particular class II loci or alleles results in specific
immunopathological and serological manifestations of disease will be
investigated.  The accomplishments of these Specific Aims will result in
important new information regarding the fundamental mechanisms of the
immunoregulation of systemic autoimmunity in MRL/lpr mice and will thus
allow us eventually to understand the parallel human syndrome of SLE.
Only with such understanding will it be possible to design new rational
therapeutic approaches.

## Key facts

- **NIH application ID:** 3155428
- **Project number:** 2R01AR026574-12A1
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **SAM.gov UEI:** D3LHU66KBLD5
- **Principal Investigator:** ROBERT A. EISENBERG
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1993
- **Award amount:** $212,039
- **Award type:** 2
- **Project period:** 1979-12-01 → 1996-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3155428

## Citation

> US National Institutes of Health, RePORTER application 3155428, MECHANISMS OF AUTOREACTIVITY IN SLE (2R01AR026574-12A1). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3155428. Licensed CC0.

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