# REARRANGEMENT OF ANTIBODY GENES IN NORMAL B CELLS

> **NIH NIH R01** · STANFORD UNIVERSITY · 1989 · $170,427

## Abstract

The major goal of this grant and its predecessor is to study normal B
lymphocyte development in the context of activation and expression of
lymphocyte-specific genes.  In the first grant the major focus was the
rearrangement of immunoglobulin heavy and light chain genes during normal B
cell development.  This study included the isolation and sequencing of the
light chain VK24 variable region gene family to determine their
evolutionary relationship.  In this proposal we expand from a study of
immunoglobulin gene expression in normal lymphocytes to include the
analysis of other B cell expressed genes.  Using the techniques lineage
tracing the growth and differentiation of pre-B cells shall be defined.  At
each stage of antigen-independent and antigen-dependent B cell
differentiation the molecular genetic events relating to the heavy chain
class switch shall be monitored on the expressed and on the nonexpressed
heavy chain chromosome.  This will require an analysis of these heavy chain
arrangements in 1) three different stages of pre-B cell development; 2) in
virgin BMu and mature B MuDelta cells; 3) in antigen-activated germinal
center B cells expressing IgG or IgA receptor immunoglobulins of either one
parental allotype or the other; and 4) in plasma cells.  The lymphocyte
differentiation antigens which are expressed in pre-B cell development
(TdT, B220), in subsets of resting mature B cells (Ly-1, B220), and in
antigen activated germinal center cells (transferrin receptor) are the
primary objects of a new cDNA cloning strategy developed in this
laboratory.  The eventual objective of this cloning strategy is to
characterize each of these genes in order to examine at the DNA sequence
level whether particular shared sequences might be involved in their
selective expression in B cells.  Finally, a complete study of VK24
(antiphosphorycholine and antistreptococcyl A carbohydrate) light chain
variable region genes will be carried out to understand their mechanism of
evolution and their current status in mouse and man.  The studies on normal
pre-B cell and B cell differentiation should highlight those potential
defects which may lead to B cell immunodeficiency syndromes.  A study of
the role of terminal transferase in  providing immunoglobulin gene
diversification during B cell differentiation will use as a model a mouse
genetic defect (motheaten) whose hallmarks are immunodeficiency and
autoimmunity.  The studies on the immunoglobulin class switch mechanism
should reveal important information for the eventual study of Ataxia
Telangiectasia and selective immunoglobulin deficiency diseases.  The
analysis of the V kappa 24 family might reveal a basis for inordinate
susceptibility to bacterial infection in certain humans.

## Key facts

- **NIH application ID:** 3127732
- **Project number:** 5R01AI018162-08
- **Recipient organization:** STANFORD UNIVERSITY
- **SAM.gov UEI:** HJD6G4D6TJY5
- **Principal Investigator:** Irving L. Weissman
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1989
- **Award amount:** $170,427
- **Award type:** 5
- **Project period:** 1981-09-30 → 1989-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3127732

## Citation

> US National Institutes of Health, RePORTER application 3127732, REARRANGEMENT OF ANTIBODY GENES IN NORMAL B CELLS (5R01AI018162-08). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3127732. Licensed CC0.

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