Heterogeneity of tonsillar subepithelial B lymphocytes, the splenic marginal zone equivalents

Mariella Dono, Simona Zupo, Nicolò Leanza, Giovanni Melioli, Manuela Fogli, Andrea Melagrana, Nicholas Chiorazzi, Manlio Ferrarini

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The V(H)4 genes expressed by both resting and in vivo-activated subepithelial (SE) B cells from human tonsils were studied. Resting SE B cells were subdivided according to the presence (IgD(low)) or absence (IgM- only) of surface IgD. CD27 was abundant on activated SE B cells and low on resting IgM-only B cells. Resting IgD(low) SE B cells could be subdivided into CD27(low) and CD27(high) cell fractions. Resting IgD(low) SE B cells displayed V(H)4 genes with a substantial number of mutations (13/29 of the molecular clones were mutated), whereas 25/26 of the clones from resting IgM- only SE B cells were unmutated. Moreover, mutated V(H)4 genes were detected mainly within the CD27(high) cell fraction of the IgD(low) SE B cells. Several identical unmutated V(H)4DJ(H) sequences (11/32) were found in different molecular clones from resting IgM-only SE B cells, suggesting local cellular expansion. Both unmutated (14/25) and mutated (11/25) sequences were found in μ transcripts of activated SE B cells. Extensive mutation was observed in the γ transcripts of activated SE B cells. Therefore, SE B cells are heterogeneous, being comprised of B cells with mutated Ig V(H)4 genes, that are Ag-experienced B cells, and a subset of B cells with unmutated V(H)4 genes that are either virgin cells or cells driven by Ags that did not induce or select for V gene mutations.

Original languageEnglish
Pages (from-to)5596-5604
Number of pages9
JournalJournal of Immunology
Issue number11
Publication statusPublished - 2000

ASJC Scopus subject areas

  • Immunology


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