# CELLULAR AND HUMORAL BASES OF MUCOSAL IMMUNE RESPONSE

> **NIH NIH R01** · UNIVERSITY OF PENNSYLVANIA · 1989 · $292,643

## Abstract

Our principle objective is to understand the cellular and molecular
mechanisms leading to the development of a mucosal immune
response.  Such a response acts to prevent, limit, contain, and
resolve bacterial and viral infections that commence via the
respiratory or gastrointestinal epithelium.  Since the IgA isotype
of antibody is primarily responsible for humoral immunity
expressed at mucosal surfaces we are particularly concerned with
the aspects of B cell development leading to antibody isotype
restriction and commitment to expression of the IgA isotype.  Our
research program has four main aims: 1) to discern those
characteristics of vaccines and adjuvants that make them
effective at stimulating and priming for a secretory antibody
response by the mucosal route; 2) to determine the cellular and
molecular requirements for stimulating IgA memory cells to
proliferate and generate clones making IgA antibodies; 3) to
assess whether germinal centers, especially those in Peyer's
patches (PP) in the walls of the gut, are sites of isotype switching,
variable region gene mutations, and diversification of B cells to
pre-memory or preplasma cells; and 4) to determine whether
mucosal follicles in respiratory and gastrointestinal tract function
tract function similarly as sites of IgA memory cell development
and whether 'cross-priming' can occur when antigen is applied to
either mucosal surface.

To address these goals we will prepare hapten-conjugates of
cholera toxin, the most efficacious non-replicating antigen known,
to stimulate a mucosal IgA response via the gut route.  These
conjugates as well as Mycoplasma pulmonis, reovirus type 1, and
Morganella morganii (a gram-negative enteric bacteria) will be
administered by the mucosal route to prime mucosal lymphoid
tissue for specific IgA responses.  Clonal murine B cell cultures
will be used to establish growth, differentiation, and regulatory
stimuli for IgA memory cells by adding subsets of T-helper cells,
dendritic cells, cytokines, Ig-binding factors, and putative
regulatory T cells.  Germinal center (GC) and non-GC PP cells
will be resolved based on MAbs and lectins that define surface
phenotypes and their functional potential will be tested in vitro
and in vivo.  Molecular genetic analyses will be used to probe for
isotype switching, point mutation, and shifts in mRNA for
secreted versus mucosal stimulation.  Both allotype congenic
immunocompetent and severe combine immunodeficient mice will
be used to assess functional potential and protective role of
subsets of GC and non-GC PP cells.

## Key facts

- **NIH application ID:** 3127616
- **Project number:** 5R01AI017997-10
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **SAM.gov UEI:** GM1XX56LEP58
- **Principal Investigator:** JOHN J CEBRA
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1989
- **Award amount:** $292,643
- **Award type:** 5
- **Project period:** 1980-09-01 → 1993-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3127616

## Citation

> US National Institutes of Health, RePORTER application 3127616, CELLULAR AND HUMORAL BASES OF MUCOSAL IMMUNE RESPONSE (5R01AI017997-10). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3127616. Licensed CC0.

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