# CHILDRENS ANTIBODIES TO POLYSACCHARIDES : V REGION GENES

> **NIH NIH R01** · WASHINGTON UNIVERSITY · 1991 · $205,520

## Abstract

The remarkable diversity of the B cell antibody repertoire is generated
through the combinatorial assortment of distinct groups of immunoglobulin
(Ig) germline elements.  Further diversification of rearranged Ig genes
is provided by a unique process of somatic hypermutation.  The individual
contribution of each of these mechanisms to the functional antibody
repertoire is unknown.  The antibody response to the capsular
polysaccharide (PS) of a major childhood bacterial pathogen, Haemophilus
influenzae type b (Hib), is restricted to a limited number of antibody
species (cl notypes).  Therefore it should serve as an excellent model to
examine the relative contribution of different germline variable (V)
regions and somatic mutation to the functional immune response.
Furthermore, susceptibility to this infection is a function of age and
may be related to the ontogeny of V gene usage.  The overall goal of this
proposal is to study the expression of the human V region gene repertoire
as a function of age and the form of antigenic exposure.  In this study
we propose 1) To isolate human antiHib PS B cells in the form of
hybridomas from infants, children and adults at various times following
immunization with T-independent (TI) and T-dependent (TD) forms of Hib PS
vaccine, 2) To determine the IgV region repertoire by sequence analysis
of cDNA clones of hybridomas and by anti-idiotype analysis of serum
antibodies and peripheral B cells, 3) To examine the relationship between
V region sequence or Ig isotype, and functional activity of anti-Hib PS
antibodies, and 4) To examine the contribution of Ig gene somatic
hypermutation to IgV region diversity in response to both TD and TI
vaccines.  The V genes of the B cell hybridoma antibodies can be readily
sequenced.  In addition, the development of V region specific
anti-idiotype antibodies will allow the analysis of a large number of
serum samples without the need to isolate, clone and sequence a large
number of hybridomas.  Comparison of V genes captured at different
timepoints following immunization will determine the contribution of V
gene usage and somatic mutation to maturation of the antibody response.
Determining the impact of somatic mutation in both TI and TD responses
will clarify the role of T cells in this unique process.  Finally,
knowledge of V region usage at different ages will determine the ontogeny
of V gene usage and  may provide clues to the susceptibility of certain
patients to this infection.

## Key facts

- **NIH application ID:** 3128722
- **Project number:** 2R01AI019350-07A1
- **Recipient organization:** WASHINGTON UNIVERSITY
- **SAM.gov UEI:** L6NFUM28LQM5
- **Principal Investigator:** PENELOPE G SHACKELFORD
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1991
- **Award amount:** $205,520
- **Award type:** 2
- **Project period:** 1982-09-01 → 1995-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3128722

## Citation

> US National Institutes of Health, RePORTER application 3128722, CHILDRENS ANTIBODIES TO POLYSACCHARIDES : V REGION GENES (2R01AI019350-07A1). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3128722. Licensed CC0.

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