# CELLULAR AND MOLECULAR EVENTS IN B LYMPHOCYTE ACTIVATION

> **NIH NIH R01** · DUKE UNIVERSITY · 1992 · $235,084

## Abstract

Mouse mammary tumor proviral (MMTV) genes are constitutively expressed
in cells of the B lineage and can be regulated during B cell
differentiation. One MMTV gene, the open reading frame (ORF) of the 3'
long terminal repeat (LTR), has been shown to encode "endogenous
superantigens". When expressed endogenously, superantigens delete T
cells expressing appropriate V Beta elements. The 3' LTR ORF also
encodes a protein(s) that is a transactivator. The function of the
transactivator is no known, but it may be important in the viral life
cycle and may contribute to the transforming potential of the virus. The
experiments outlined in this proposal are designed to characterize the
regulation of MMTV gene expression in cells of the B lineage, and to
determine the function(s) of LTR-derived proteins. We will evaluate the
regulation of superantigen expression in B lymphocytes, and determine at
what level(s) the functional expression of superantigens is post-
translationally regulated. We will determine the structural and cellular
requirements for functional transactivation by the MMTV 3' LTR ORF, and
determine if transactivation is a B cell restricted effect or requires
association of the 3' LTR protein and class II molecules. We will assess
the relationship between the proteins that are responsible for
transactivation and superantigen activities. We will characterize the
cellular genes that are transactivated in B cells, and determine the
intermediary protein(s) through which transactivation is mediated. We
will characterize the cis-regulatory sequences in the U3 region of the
MMTV LTR which control constitutive and upregulated gene expression in
LPS and IL-5 stimulated B cells, and determine of the proteins which
bind these sequences are similar to other known transcriptional
regulatory proteins. We will determine the role of the immune system in
the MMTV life cycle, testing the hypothesis that interactions between
superantigen reactive T cells and virally infected B cells are required
for the horizontal transmission of the virus in infected mice. Finally,
we will use transfected cells and transgenic mice constitutively
expressing the 3' LTR ORF gene to determine if other protooncogenes
cooperate with this MMTV encoded gene in cellular transformation. The
studies proposed in this application will address issues concerning the
biology of B lymphocytes, the interactions of viruses with cells of the
immune system, and fundamental problems concerning the nature of
transactivating proteins, transformation, and oncogenesis.

## Key facts

- **NIH application ID:** 3174241
- **Project number:** 2R01CA036642-12
- **Recipient organization:** DUKE UNIVERSITY
- **SAM.gov UEI:** TP7EK8DZV6N5
- **Principal Investigator:** RONALD B CORLEY
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1992
- **Award amount:** $235,084
- **Award type:** 2
- **Project period:** 1987-07-01 → 1995-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3174241

## Citation

> US National Institutes of Health, RePORTER application 3174241, CELLULAR AND MOLECULAR EVENTS IN B LYMPHOCYTE ACTIVATION (2R01CA036642-12). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3174241. Licensed CC0.

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