# MURINE MODELS OF GENERALIZED AUTOIMMUNITY

> **NIH NIH R01** · SCRIPPS CLINIC AND RESEARCH FOUNDATION · 1987 · $284,478

## Abstract

Mice with spontaneous lupus erythematosus- and rheumatoid arthritis-like
manifestations are characterized by B cell hyperactivity,
hypergammaglobulinemia and autoantibodies against a variety of
self-antigens, particularly nuclear antigens and IgG.  These autoantibodies
appear to be central to disease, forming immune complexes which damage
various organs.  This proposal focuses on defining, at the clonal level,
the molecular generation and structure of these effector molecules.
Libraries of monoclonal autoantibody-producing hybridomas will be developed
from different genetic background mice with spontaneous lupus/arthritis,
and mice with experimentally-induced autoantibody production.  The
libraries will be screened with nucleic acid probes to define the usage
patterns of VH-VL, gene families, joining (J), and
complementarity-determining region (CDR) elements.  Correlations with
autoantibody isotype, antigenic specificity, strain of origin and means of
induction will be made.  mRNAs encoding heavy (H) and light (L) chains of
selected monoclonal autoantibodies and the germline V genes from which they
derive will be molecularly cloned, and complete nucleotide sequences of
VH-DH-JH and VL-JL elements determined to define the genetic elements
encoding their production, their relation to the respective germline
elements and the involvement of somatic mutation in autoantibody
generation.  The contribution of germline genes to autoantibody specificity
will be further examined by transfecting cells with functionally-rearranged
germline and/or specifically mutagenized V genes, and assaying the
expressed Ig products for autoantibody activity.  Anti--idiotypic reagents
against synthetic peptides from the autoantibodies' CDRs and molecular V
region-specific probes will be prepared and used to define the extent of
the autoantibody repertoire and the preponderance of certain idiotypes in
sera and afflicted tissues, and thus the relationship of autoantibody
structure with pathogenicity.  These studies at the clonal level will allow
definitive conclusions on the relationship of autoantibody structure to
pathogenicity, their origin and regulation, and clarify the role of
germline and somatic diversification mechanisms in autoimmune pathogenesis.

## Key facts

- **NIH application ID:** 3155992
- **Project number:** 5R01AR031203-05
- **Recipient organization:** SCRIPPS CLINIC AND RESEARCH FOUNDATION
- **Principal Investigator:** Argyrios N Theofilopoulos
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1987
- **Award amount:** $284,478
- **Award type:** 5
- **Project period:** 1983-04-01 → 1991-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3155992

## Citation

> US National Institutes of Health, RePORTER application 3155992, MURINE MODELS OF GENERALIZED AUTOIMMUNITY (5R01AR031203-05). Retrieved via MORVS 2026-10-24 from https://api.morvs.ai/grant/nih/3155992. Licensed CC0.

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