# MECHANISMS OF LYMPHOCYTE-ANTIGEN INTERACTIONS

> **NIH NIH R01** · WALTER AND ELIZA HALL INST MEDICAL RES · 1989 · $81,445

## Abstract

All immune responses depend on antigens stimulating specific
lymphocyte cells to become activated.  This process involves a
small, non-dividing cell enlarging, dividing several times, and
building a secretory factory in the cytoplasm.  For the B
lymphocyte, the secreted product is an antibody.  for an immune
response to be appropriate to the stimulus, be this an infection or
a vaccination, every step in this elaborate activation pathway
needs to be controlled or fine-tuned.  Our research aims to dissect
the steps of activation and thus to understand the cellular
mechanisms underlying antibody formation.  This understanding
will help the design of new and improved vaccines, and will allow
deeper insights into autoimmune diseases.

B lymphocytes will be obtained from the spleens and other
lymphoid organs of mice.  They will be fractionated by procedures
that allow the isolation of cells predestined to form antibody only
to a particular antigen of choice.  Through microculture
techniques, these antigen-specific B cells will be cultured as
single cells over a 5 to 6-day period.  They will be stimulated by
controlled amounts of the antigen with which they are reactive,
aided by one or more pure growth factors called interleukins or
IL.  Specifically, IL-4, IL-5, IL-6, IL-1 and IL-2 will be used both
as single agents and in various permutations and combinations.
Activation of single small B cells will be monitored
microscopically through measured enlargement.  Division will be
noted through repeated microscopy.  Antibody formation will be
studied by assay of the microculture fluid, both for amount and
for chemical kind or isotype".

The project will have 4 linked aims.  First, we shall establish
exactly which phase of the activation cascade is controlled by
which interleukin.  Secondly, we will study mice that have been
"tricked" into treating the foreign antigen as though it were part
of the body itself (i.e. rendered immunologically tolerant) in the
hope of defining more precisely the cellular mechanisms for self-
recognition.  Thirdly, we will examine different varieties (subsets)
of B lymphocytes to see how and why they respond differentially
to activation signals.  Fourthly, we will investigate the regulated
appearance and disappearance of specific protein receptors at the
B cell surface for the various interleukins that control their
growth and development.

## Key facts

- **NIH application ID:** 3124162
- **Project number:** 5R01AI003958-28
- **Recipient organization:** WALTER AND ELIZA HALL INST MEDICAL RES
- **SAM.gov UEI:** ZVG2YKNTQPB9
- **Principal Investigator:** GUSTAV J NOSSAL
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1989
- **Award amount:** $81,445
- **Award type:** 5
- **Project period:** 1978-06-01 → 1991-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3124162

## Citation

> US National Institutes of Health, RePORTER application 3124162, MECHANISMS OF LYMPHOCYTE-ANTIGEN INTERACTIONS (5R01AI003958-28). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3124162. Licensed CC0.

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