# SEROLOGIC CELLULAR & MOLECULAR STUDIES OF AUTOANTIBODIES

> **NIH NIH R01** · NORTH SHORE UNIVERSITY HOSPITAL · 1992 · $236,823

## Abstract

The long-term goal of this proposal is to understand the relationship
between "naturally-occurring" and "disease-related" autoantibodies in man.
The former are polyreactive, low affinity, IgM antibodies produced by CD5+
B cells that have non-mutated Ig V genes, presumably because of a lack of
T cell-stimulated, antigen-driven maturation.  In contrast, disease-related
autoantibodies are monoreactive, higher affinity IgM or IgG antibodies
whose cellular origin has not been exclusively assigned to either the CD5+
or CD5- subsets.  Based on animal experiments, these antibodies are
products of cells that are clonally selected and have highly mutated V
genes.  However, human experiments have failed to demonstrate evidence for
V gene somatic mutation.  This may relate to the lack of availability of B
cell lines making true disease-related autoantibodies.  We will try to
solve this dilemma by studying the B cells and IgM and IgG rheumatoid
factors (RF) from rheumatoid arthritis (RA) and hypergammaglobulinemic
purpura (HGGP) patients and comparing these with comparable cells and
antibodies from normal neonates and adults.  B cells will be taken from
umbilical cord blood, and from the major sites of autoantibody synthesis in
these diseases: the synovium in RA and the spleen in HGGP.

CD5+ and CD5- B cells from these sources will be subcategorized:
phenotypically by the expression of mutation and activation antigens;
functionally by their T cell dependencies, cytokine responsiveness, and
autoantibody synthesis; and genetically by Ig V/H gene family usage and RF
cross-reactive idiotype (CRI) expression.  Based on these subcategorization
data, we will expand those B cell subsets that make disease-related
autoantibodies, some of which will be immortalized by EBV transformation
and/or somatic cell hybridization.  These populations, and those generated
during the previous granting period that make natural autoantibodies, will
be used for Ig V/H and V/L gene DNA sequencing studies.  Sequencing will be
facilitated by suing a PCR technique that employs a series of
oligonucleotide primers spanning the known upstream leader and downstream
C region sequence.  Finally, the autoantibodies produced by these cell
lines will be analyzed for their antigen-binding specificities, affinities,
and CRIs, and these immunologic characteristics compared with the DNA
sequences to determine the molecular bases for their expression.

## Key facts

- **NIH application ID:** 3124824
- **Project number:** 5R01AI010811-25
- **Recipient organization:** NORTH SHORE UNIVERSITY HOSPITAL
- **Principal Investigator:** Nicholas Chiorazzi
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1992
- **Award amount:** $236,823
- **Award type:** 5
- **Project period:** 1987-05-01 → 1995-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3124824

## Citation

> US National Institutes of Health, RePORTER application 3124824, SEROLOGIC CELLULAR & MOLECULAR STUDIES OF AUTOANTIBODIES (5R01AI010811-25). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3124824. Licensed CC0.

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