# DNA SEQUENCES INVOLVED IN THE HEAVY CHAIN SWITCH

> **NIH NIH R01** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 1988 · $160,513

## Abstract

During antigen-driven differentiation of immunoglobulin-
producing cells, a switch from mu to gamma, epsilon, or a heavy
chain synthesis can occur.  This protein switch is the result of a
DNA deletion that moves a V region from a donor C mu to a C
gamma, C epsilon, or C alpha gene.  This deletion begins and ends
in switch segments, DNA regions composed of tandemly repeated
sequences.  We propose to molecularly clone and sequence the
switch recombination sites in six to ten rearranged gamma 3 and
gamma 1 genes from hybridoma DNA.  The gamma 3 and gamma 1
switch regions each include a characterisitic 49 base pair
tandemly repeated sequence.   Our previous data indicate that the
gamma 3 switches are uniformly distributed throughout its 49mer
consensus sequence, but that the S gamma 1 switches are
localized to a part of its 49mers consensus sequence.
Furthermore, sequences near gamma switch sites suggest that a
single enzyme may mediate the cutting/religation for all four
gamma genes in the mouse.  We will use our new sequence data
from gamma switch sites to test these tentative conclusions.  We
will determine if switch recombination occurs in the tandemly
repeated sequences only, or if it can occur in non-49mer
sequences in the S gamma 1 region.  We will also use data derived
from nucleotide sequences of cloned switch regions to understand
any correlative relationships in switch sites on the two
chromosomes from a single immunoglobulin expressing cell.
Under the same group of experiments, we will examine the
structure of rearranged switch regions from cells with simple
switching patterns (typical switches) and complex switching
patterns (atypical switches).  We will also examine the switch
region content of murine hybridomas generated using an alpha-
expressing myeloma partner.  We will ask if the two spleen cell-
derived Igh loci tend to rearrange to the same switch region, and
indication of isotype specificity in the heavy chain switch
recombinational event.  So that we might understand the DNA
sequence recognition, specificity, and genetics of switch
recombinases we  propose to select a cell line that constitutively
produces these enzymes.

## Key facts

- **NIH application ID:** 3177820
- **Project number:** 5R01CA039068-08
- **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:** 1988
- **Award amount:** $160,513
- **Award type:** 5
- **Project period:** 1984-09-01 → 1992-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3177820

## Citation

> US National Institutes of Health, RePORTER application 3177820, DNA SEQUENCES INVOLVED IN THE HEAVY CHAIN SWITCH (5R01CA039068-08). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3177820. Licensed CC0.

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