# ASSEMBLY AND EXPRESSION OF IG VARIABLE REGION GENES

> **NIH NIH R01** · COLUMBIA UNIV NEW YORK MORNINGSIDE · 1988 · $210,246

## Abstract

We propose to exploit technologies and systems that we have developed to
analyze in detail the molecular mechanisms involved with the somatic
generation of the antibody repertoire.  Specifically:  1. We have designed
recombination substrate/gene transfer experiments to test details of the V
gene assembly mechanism and similar types of experiments to elucidate the
molecular mechanisms which regulate variable region gene assembly; a
particular focus of the latter studies is the notion that tissue and stage
specific assembly of VH, VL, and VT (T cell receptor) genes is regulated at
the level of accessibility to a common recombinase.  Ultimately, the
mechanisms defined from the cell culture studies will be further elucidated
by transgenic mouse methodologies.  2. We have demonstrated that germline
VH gene expression occurs specifically in immature pre-B cells.  The
function of V gene expression will be investigated by elucidating the
involved regulatory sequences, by searching for analogous expression of VL
genes, and by identifying the nature and cellular location of putative VH
proteins.  3. We have demonstrated that the most 3' VH gene segments are
used highly preferentially by developing pre-B cells of Balb/c mice.  To
understand the role of this phenomenon in B cell development, we will
extend these analyses to light chain V genes and to the development of the
variable region gene repertoire in other mouse strains, including
immunodeficient or autoimmune mice.  We will also determine the factors
which lead to normalization of the VH repertoire in adult mice.  To
facilitate these and other studies, we will continue to develop in situ
RNA/RNA hybridization method to assay specific Ig gene expression in normal
B lineage cells.  To complete our analyses of VH gene usage, we will
further define the structure and linkage of the most 3' VH family and the D
families by a combination of cosmid cloning and pulsed field gradient gel
electrophoresis methodologies.  4. Finally, we have identified a pre-B cell
specific proto-oncogene; we will now use methods that we have developed to
isolate, define, and characterize other gene products that are specific for
the early stages of B cell development.

## Key facts

- **NIH application ID:** 3129530
- **Project number:** 5R01AI020047-06
- **Recipient organization:** COLUMBIA UNIV NEW YORK MORNINGSIDE
- **SAM.gov UEI:** F4N1QNPB95M4
- **Principal Investigator:** Frederick W. Alt
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1988
- **Award amount:** $210,246
- **Award type:** 5
- **Project period:** 1983-04-01 → 1991-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3129530

## Citation

> US National Institutes of Health, RePORTER application 3129530, ASSEMBLY AND EXPRESSION OF IG VARIABLE REGION GENES (5R01AI020047-06). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3129530. Licensed CC0.

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