Heterogeneity of tonsillar subepithelial B lymphocytes, the splenic marginal zone equivalents.
The VH4 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 (IgDlow) or absence (IgM-only) of surface IgD. CD27 was abundant on activated SE B cells and low on resting IgM-only B cells. Resting IgDlow SE B cells could be subdivided into CD27low and CD27high cell fractions. Resting IgDlow SE B cells displayed VH4 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 VH4 genes were detected mainly within the CD27high cell fraction of the IgDlow SE B cells. Several identical unmutated VH4DJH 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 VH4 genes, that are Ag-experienced B cells, and a subset of B cells with unmutated VH4 genes that are either virgin cells or cells driven by Ags that did not induce or select for V gene mutations.
Dono
M
M
Servizio di Immunologia Clinica and Servizio di Citometria Centro Biotechnologie Avanzate, Istituto Nazionale per la Ricerca sul Cancro, IST, Genova, Italy. mdono@hp380.ist.unige.it
Zupo
S
S
Leanza
N
N
Melioli
G
G
Fogli
M
M
Melagrana
A
A
Chiorazzi
N
N
Ferrarini
M
M
D016175:B-Lymphocyte Subsets / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D004848:Epithelium; D005786:Gene Expression Regulation / Q000276:immunology; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain; D018095:Germ-Line Mutation / Q000276:immunology; D018858:Germinal Center / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007072:Immunoglobulin D / Q000096:biosynthesis; D007075:Immunoglobulin M / Q000096:biosynthesis; D007135:Immunoglobulin Variable Region / Q000096:biosynthesis / Q000235:genetics; D016130:Immunophenotyping; D007399:Interphase / Q000235:genetics / Q000276:immunology; D008213:Lymphocyte Activation / Q000235:genetics; D008969:Molecular Sequence Data; D014066:Palatine Tonsil / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D013154:Spleen / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000096:biosynthesis
D007072:Immunoglobulin D; D007075:Immunoglobulin M; D007135:Immunoglobulin Variable Region; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7