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

The V(H)4 genes expressed by both resting and in vivo-activated subepitheli al (SE) B cells from human tonsils were studied, Resting SE B cells were su bdivided according to the presence (IgD(low)) or absence (Ig M-only) of sur face 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 clon es were mutated), whereas 25/26 of the clones from resting IgM-only SE B ce lls were unmutated, Moreover, mutated V(H)4 genes were detected mainly with in the CD27(high) cell fraction of the IgD(low) SE B cells. Several identic al unmutated V(H)4DJ(H) sequences (11/32) were found in different molecular clones from resting IgM-only SE B cells, suggesting local cellular expansi on. Both unmutated (14/25) and mutated (11/25) sequences were found in mu t ranscripts of activated SE B cells. Extensive mutation was observed in the gamma transcripts of activated SE B cells. Therefore, SE B cells are hetero geneous, being comprised of B cells with mutated Ig V(H)4 genes, that are A g-experienced B cells, and a subset of B cells with unmutated V(H)4 genes t hat are either virgin cells or cells driven by Ags that did not induce or s elect for V gene mutations.