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D A Lebman

Publications and source records attributed to D A Lebman.

24 records · Page 2Linked to original sources
PubMed1987

Relationship between expression of IgA by Peyer's patch cells and functional IgA memory cells.

IgA memory B cells have been operationally defined as precursors that give rise to clones exclusively secreting IgA antibodies upon antigen stimulation in a T-cell dependent splenic fragment culture. B lymphocytes that are sIgA+ account for a small fraction of Peyer's patch lymphocytes, but these can be clearly divided into two subsets. One subset contains the majority of sIgA+ B cells and most of these are in S, G2, or M phase of the cell cycle. These cells are germinal center B cells, as defined by being S kappa low and peanut agglutinin (PNA)high, and contain most of the mRNA alpha. Though these germinal center cells may contain the majority of sIgA+ B cells and may contain precursors for memory cells, preplasma cells, or both, they do not appear to be immediately responsive to stimulation by antigen. Rather, the S kappa high, PNAlow subset of sIgA+ B cells, most of which are in G0 or G1 and have only low levels of mRNA alpha appear to contain most of the clonal precursors that are committed to IgA, i.e., the functional memory cells that give rise to clones exclusively secreting IgA upon stimulation with thymus-dependent antigen in the presence of T cells. There is also a population of Peyer's patch B cells that neither bears detectable sIgA nor has mRNA alpha detectable by cytoplasmic dot blotting but contains a small proportion of the functional IgA memory cells.

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PubMed1986

CH isotype switching in B cell differentiation.

We have functionally defined a number of B cell subsets that likely represent B cells at different stages of development, based on the pattern of CH isotypes expressed by their clones in splenic fragment or microcultures and on those factors necessary in culture to support the growth of a clone displaying a particular isotype or set of isotypes. Our observations are consistent with isotype switching being a stochastic process which results in the occurrence of progressive isotype restriction in members of a diversifying clone. The surface marker best predictive of the pattern of isotypes a clone may secrete is the sIg isotype of its B cell precursor. Those B cells that have switched to the expression of non-IgM isotypes in vivo can be stimulated in vitro in splenic fragments to give an antibody-secreting clonal culture but so far cannot be stimulated in a microculture of dispersed cells that supports clones secreting IgM alone or with other isotypes.

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PubMedDate not supplied

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.

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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