# GENETICS AND REGULATION OF THE IG VH REGION

> **NIH NIH R01** · FLORIDA STATE UNIVERSITY · 1987 · $117,590

## Abstract

An understanding of the mechanisms involved in the generation of antibody
diversity to the tremendous variety of antigens and potential pathogens has
long been a major goal of immunologists.  It is now known that each of the
l00 or so VH genes are theoretically able to associate with each of several
D and JH genes to generate H-chain diversity.  This combinatorial diversity
is augmented by junctional diversity, somatic mutation, the insertion of
additional nucleotides at junctions (N segments) and possibly gene
conversion.

The relative contribution of the various diversity generating mechanisms to
an immune response is poorly understood, as is the extent of the reserve
diversity potential.  To address these questions, a unique model system
will be used in which a set of VH genes which ordinarily makes only a very
minor contribution to the total array of Ig molecules will be forced to
generate the entire VH contribution to the immune defense of the organism,
thus revealing the full diversity-generating potential of these genes.
Lymphoid tissue from a rabbit permitted (through allotype suppression) to
express only a few VH genes will be processed to yield both Mu and Gamma VH
cDNA libraries form H-chain mRNA.  A germline DNA library will also be
constructed using nonlymphoid tissues from the same rabbit.  Selected
cloned cDNAs will be sequenced for comparison to each other and to their
progenitor germline genes to assess the relative contributions and possible
interrelationships of somatic mutation, gene conversion, D and JH
associations with VH, or other diversity-generating mechanisms to diversity.

The contribution of germline genes and the diversity-generating mechanisms
to the expressin of latent allotypes will also be investigated.  Latent
allotypes appear to be genetically unexpected VH regions which occur
spontaneously at low levels in some rabbits.  Latent allotypes can also be
reliably induced in all rabbits thus far tested through the injection of
anti-allotype antibody.  It has been postulated that latent allotypes may
play a role in a pre-existing allotype/idiotype regulatory network.

The VH region from latent al IgG will be first sequenced at the protein
level.  This information will be used to construct oligonucleotide probes
to be used to identify the corresponding cDNA and germline genes.

## Key facts

- **NIH application ID:** 3126722
- **Project number:** 5R01AI016596-08
- **Recipient organization:** FLORIDA STATE UNIVERSITY
- **SAM.gov UEI:** JF2BLNN4PJC3
- **Principal Investigator:** KENNETH H ROUX
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1987
- **Award amount:** $117,590
- **Award type:** 5
- **Project period:** 1979-12-01 → 1991-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3126722

## Citation

> US National Institutes of Health, RePORTER application 3126722, GENETICS AND REGULATION OF THE IG VH REGION (5R01AI016596-08). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3126722. Licensed CC0.

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