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

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 (Ig M-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 mu transcripts of activated SE B cells. Extensive mutation was observed in the gamma 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.