# REGULATION OF B LYMPHOCYTE PROLIFERATION BY ANTIGEN

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 1991 · $201,046

## Abstract

B lymphocytes synthesize antibodies both as secreted proteins and as cell
surface receptors for antigen.  Crosslinkage of the membrane form of
immunoglobulin (mIg) results in triggering of hydrolysis of
phosphoinositides and the generation of second messengers including
diacylglycerol and cytoplasmic free calcium ions.  The goals of this
project are: 1.) to determine how mIg activates the phospholipase C enzyme
that breaks down the phosphoinositides.  This involves identifying and
characterizing the phospholipase C, the G protein that mediates between mIg
and phospholipase C, and putative accessory proteins that associate with
crosslinked mIg and permit interaction with the G protein.  A better
understanding of the molecular mechanisms of mIg signal transduction should
give us better insight into what molecular structures make particularly
good or poor antigens, which would aid vaccine design.  2.) to determine
whether phosphoinositide signaling reactions mediate the biological
response of a B lymphoma cell line that is a model for an immature B cell
undergoing tolerance induction.  Phosphoinositide breakdown will be
specifically interrupted by microinjection of antibodies that bind to these
phospholipids or by genetic knockout of phospholipase C.  In addition,
other receptors that can trigger phosphoinositide breakdown will be
introduced into the cell line by DNA-mediated gene transfer, with the
expectation that they will also induce the growth inhibitory response
normally induced by mIg, provided these signaling reactions actually
mediate the growth inhibition.  3.) to examine the mechanisms by which
phosphoinositide second messengers regulate the growth of B cells.  These
experiments will involve isolation of genes induced by mIg signal
transduction, characterization of which second messengers are responsible
for this induction, and use of these genes as molecular markers for
characterizing the defects in mutants that have lost the growth inhibitory
response to mIg signaling.  4.) to determine whether phosphoinositide
breakdown is also triggered by mIg in authentic immature B cells undergoing
tolerance induction, and whether these biochemical reactions are mediating
the response here as well.  These latter studies should give us additional
insight into the process of "clonal deletion" whereby self-reactive
lymphocytes are removed at an immature stage of their development.  The
failure of this process may play a role in the etiology of autoimmune
diseases.

## Key facts

- **NIH application ID:** 3129520
- **Project number:** 5R01AI020038-08
- **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:** 1991
- **Award amount:** $201,046
- **Award type:** 5
- **Project period:** 1984-01-01 → 1994-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3129520

## Citation

> US National Institutes of Health, RePORTER application 3129520, REGULATION OF B LYMPHOCYTE PROLIFERATION BY ANTIGEN (5R01AI020038-08). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3129520. Licensed CC0.

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