# REGULATION OF B LYMPHOCYTE PROLIFERATION BY ANTIGEN

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 1988 · $159,082

## Abstract

The development and activation of B lymphocytes is regulated by
the antigen receptors, the membrane forms of IgM and IgD.
Recently we and others have shown that crosslinkage of mIgM
with anti-IgM antibodies (presumably acting as a surrogate for
antigen) stimulates the hydrolysis of phosphatidylinositol 4,5-
bisphosphate.  This reaction generates two second messengers,
diacylglycerol, which activates protein kinase C, and inositol
1,4,5-triphosphate (IP3), which causes release of Ca++ into the
cytoplasm.  First, the molecular mechanism by which mIgM
stimulates these reactions will be examined.  The part of mIgM
involved in signal transduction will be determined by site-specific
mutagenesis of the mu gene, and the possible involvement of a
new member of the G protein coupling component family will be
assessed.  Efforts will be made to achieve mIgM activation of the
G protein and the phospholipase C in isolated membranes, as a
step toward dissecting the system.

These experiments will be done in a B cell lymphoma, WEHI-231,
which stops growing in response to anti-IgM.  The biological roles
of the second messengers generated by anti-IgM will be examined
by using phorbol diesters to mimic diacylglycerol and calcium
ionophores to increase cytoplasmic calcium and by determining
their ability to cause growth arrest in an authentic way.  If these
two small molecules are not completely responsible for growth
arrest, then IP3 may play an important role in addition to causing
Ca++ release.  Recently it has been shown that 1,4,5 IP3 can be
converted to 1,3,4 IP3, a more long-lived compound.  The kinetics
and regulation of production of these two isomers of IP3 will be
characterized by using HPLC separations.  One advantage of the
WEHI-231 system is that mutants defective in the signaling or in
the growth regulation have been obtained.  Many of the
experiments described above will be used to determine the nature
of the defect in each of the mutants.  This may give us
considerable insight into the mechanisms of signal transduction
and/or growth regulation.  Finally, the nature of the growth
regulation of these cells by anti-IgM will be probed by introducing
several known oncogenes into WEHI-231 cells and examining the
effects they have on growth regulation and anti-IgM-stimulated
phosphoinositide breakdown.  For example, the ras and src
oncogenes have been proposed to affect the phosphoinositide
pathway, and this will be examined in transfected WEHI-231 cells.

## Key facts

- **NIH application ID:** 3129518
- **Project number:** 5R01AI020038-05
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **SAM.gov UEI:** KMH5K9V7S518
- **Principal Investigator:** Anthony L Defranco
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1988
- **Award amount:** $159,082
- **Award type:** 5
- **Project period:** 1984-01-01 → 1989-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3129518

## Citation

> US National Institutes of Health, RePORTER application 3129518, REGULATION OF B LYMPHOCYTE PROLIFERATION BY ANTIGEN (5R01AI020038-05). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3129518. Licensed CC0.

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