# DNA SEQUENCES INVOLVED IN THE HEAVY CHAIN SWITCH

> **NIH NIH R01** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 1993 · $184,685

## Abstract

Early in an immune response, the predominant immunoglobulin heavy chain
produced is mu, later in the immune response the predominant immunoglobulin
heavy chain is gamma, alpha, or epsilon.  This change in heavy chain usage
is accomplished by a DNA rearrangement that moves the heavy chain variable
region gene from the mu constant region to the alpha constant region,
epsilon constant region, or to one of the four gamma gamma1, gamma2b,
gamma2a, or gamma3 in mouse) constant regions.  This DNA rearrangement
involves segments of DNA (called switch segments) upstream of each constant
region gene.  Immunoglobulin producing cells have a choice of six different
switch rearrangements.  This choice is an important one; the seven
different heavy chain constant regions mediate very different effector
functions and so handle an infectious organism or its toxic products in
very different ways.  Previous results have demonstrated that this choice
is not random in the immunoglobulin producing cell, but rather is
regulated.  Furthermore, it seems likely that the regulation is mediated by
changes in the local structure of chromatin of specific switch regions.
The overall goal of the proposed experiments is to understand the molecular
mechanisms by which switch recombination is regulated in a gene specific
way.  We plan to identify nuclear proteins that might control heavy chain
gene-specific rearrangement and to identify the DNA sequences to which they
bind.  The candidate regulatory DNA sequences will be tested for their
ability to alter chromatin/DNA structure by measuring changes in
transcription mediated by the DNA sequences.  The DNA sequences will be
tested by transient transfection of cells that produce and do not produce
immunoglobulin, and by transient transfection of cells that will be treated
in various ways to induce gene-specific recombination.  We will test the
ability of the same sequences to regulate transcription from DNA molecules
inserted into transgenic mice.  Finally, we will attempt to test the
ability of the sequences to regulate switch recombination from DNA
molecules introduced into transgenic mice.  We will study two murine heavy
chain genes, gamma1 and gamma2a, and two inducers of switch recombination,
IL4 for gamma1 and interferon-gamma for gamma2a.

## Key facts

- **NIH application ID:** 3177824
- **Project number:** 5R01CA039068-13
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **SAM.gov UEI:** GNJ7BBP73WE9
- **Principal Investigator:** Wesley A. Dunnick
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1993
- **Award amount:** $184,685
- **Award type:** 5
- **Project period:** 1984-09-01 → 1997-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3177824

## Citation

> US National Institutes of Health, RePORTER application 3177824, DNA SEQUENCES INVOLVED IN THE HEAVY CHAIN SWITCH (5R01CA039068-13). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3177824. Licensed CC0.

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