# MECHANISMS OF LYMPHOCYTE-ANTIGEN INTERACTIONS

> **NIH NIH R01** · WALTER AND ELIZA HALL INST MEDICAL RES · 1992 · $99,469

## Abstract

The long term objective of this project is to understand how antigens can,
depending on circumstances, have two opposing effects on B lymphocytes, on
the one hand acting to activate the cell into proliferation and
differentiation to end up as an antibody-forming clone; or, on the other
hand, to transmit a negative signal to the B cell which may actually kill
it or temporarily inactivate it.  In other words, we seek to understand the
rules of immune induction and tolerance induction.  Insights gained will
be relevant not only to the design of new vaccination strategies, but also
to areas such as autoimmune diseases and organ transplantation.

B lymphocytes will be obtained from the spleens and other lymphoid organs
of mice.  They will be fractionated by flow cytometry and/or antigen
affinity procedures into subsets of various sorts, e.g. on the basis of
antigenic specificity, idiotypic specificity, immunoglobulin receptor
isotype spectrum, intensity of expression of B cell markers and
light-scattering characteristics.  Selected single B cells will be placed
into specialized microcultures and stimulated with antigens, mitogens and
interleukins in various combinations.  The amount, specificity, and isotype
distribution of the antibody formed will be measured by clonal
enzyme-linked immunosorbent assays (ELISA).  The immunoglobulin V genes
expressed by given clones or single cells will be determined by the
polymerase chain reaction (PCR) with special emphasis on V gene
hypermutations.  The helper and suppressor effects of certain T cells on
clonal microcultures will be measured.  We vill determine the activation
requirements of different B cell subsets, such as unimmunized, primed,
recirculating, or Ly-1 B cells.  We shall study when the somatic V gene
hypermutation process so vital to the development of high affinity B cells
commences.  We will dissect the cellular basis of immunologic tolerance
induced in adult mice by soluble, deaggregated antigens exploring the
relative contributions of T cell-mediated suppression and direct effects
of the antigen in causing anergy in the B cell itself.  If antigen-specific
suppression is a major contributor to adult tolerance, we shall ask whether
the suppressor cell secretes lymphokines which antagonize the activating
action of other lymphokines made by helper T cells.

## Key facts

- **NIH application ID:** 3124164
- **Project number:** 5R01AI003958-31
- **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:** 1992
- **Award amount:** $99,469
- **Award type:** 5
- **Project period:** 1978-06-01 → 1994-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3124164

## Citation

> US National Institutes of Health, RePORTER application 3124164, MECHANISMS OF LYMPHOCYTE-ANTIGEN INTERACTIONS (5R01AI003958-31). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3124164. Licensed CC0.

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