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Intraduodenal application of cholera holotoxin increases the potential of clones from Peyer's patch B cells of relevant and unrelated specificities to secrete IgG and IgA.

Authors
  • Lebman, D A
  • Fuhrman, J A
  • Cebra, J J
Type
Published Article
Journal
Regional immunology
Publication Date
Jan 01, 1988
Volume
1
Issue
1
Pages
32–40
Identifiers
PMID: 3275128
Source
Medline
License
Unknown

Abstract

Although it has been established that cholera toxin is both an effective mucosal immunogen and adjuvant, the mechanism by which it acts has not been determined. The relative contributions of the pharmocologic and binding capacities of holotoxin have been assessed by comparing holotoxin, acid dissociated B subunit, and B subunit from the Texas Star variant, which is deficient in production of the A subunit, for their ability to generate toxin-specific precursors in vivo that give rise to clones secreting exclusively IgA in vitro. In this way we demonstrated that although B subunit is as immunogenic as the holotoxin, pharmacologic activity appears to play a role in the generation of IgA-committed precursors. In addition, intraduodenal (i.d.) application of holotoxin can act to alter the isotype display of previously primed B cells in Peyer's patches (PP) specific for a chemically unrelated hapten resulting in an increase in the proportion of their clones that secrete IgA or IgG and a decrease in the proportion that secrete IgM following antigen-dependent in vitro clonal expansion. Intraduodenal application of cholera toxin did not appear to nonspecifically increase the proportion of IgA-committed precursors as judged by staining for sIgA and mRNA alpha levels. However, following i.d. application of cholera toxin, an overall downward shift in the levels of sIgD and s kappa was observed in the PP B cell population. We suggest that the holotoxin can nonspecifically affect the isotype display of PP B cells by altering their responsiveness to the stimuli present in the in vitro cultures.

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