title: Comparable impact of mutational and selective influences in shaping the expressed repertoire of peripheral IgM+/CD5- and IgM+/CD5+ B cells.
abstract: Somatic hypermutation and subsequent selection play a significant role in shaping the peripheral B cell repertoire. This repertoire is composed of CD5+ (5%) and CD5- B cells (95%) which are known to traffic through different lymphoid compartments. Previous studies have shown that V(H) gene usage by CD5+ and CD5- B cells is similar, although mutations are more frequent in the latter. However, the effect of mutation and subsequent selection on the expressed V(H) repertoire of CD5+ and CD5- B cells has not been delineated in detail. This study, therefore, analyzed the mutational pattern of individual IgM+/CD5+ and IgM+/CD5- B cells. In both populations, mutations can occur without heavy chain isotype switching. Despite the differences in mutational frequency, the patterns of mutation and subsequent selection were comparable in CD5+ and CD5- B cells. These results imply that although mutations are more frequent in CD5- B cells, the overall mechanisms governing somatic hypermutation and subsequent positive and negative selection are similar in CD5+ and CD5- B cells.
authors.affiliation: Department of Internal Medicine, University of Texas Southwestern Medical Center at Dallas 75235-8884, USA.
authors.forename: T
authors.initials: T
authors.lastname: Dörner
authors.forename: H P
authors.initials: HP
authors.lastname: Brezinschek
authors.forename: S J
authors.initials: SJ
authors.lastname: Foster
authors.forename: R I
authors.initials: RI
authors.lastname: Brezinschek
authors.forename: N L
authors.initials: NL
authors.lastname: Farner
authors.forename: P E
authors.initials: PE
authors.lastname: Lipsky
mesh_terms: D000225:Adenine; D000328:Adult; D016175:B-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism*; D018956:CD5 Antigens / Q000235:genetics*; D003062:Codon / Q000235:genetics; D003596:Cytosine; D004252:DNA Mutational Analysis / Q000706:statistics & numerical data; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain / Q000235:genetics; D006147:Guanine; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000096:biosynthesis / Q000235:genetics; D007133:Immunoglobulin Joining Region / Q000096:biosynthesis / Q000235:genetics; D007075:Immunoglobulin M / Q000235:genetics*; D007135:Immunoglobulin Variable Region / Q000096:biosynthesis / Q000235:genetics; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D011685:Purine Nucleotides / Q000235:genetics; D012694:Serine / Q000235:genetics; D018709:Statistics, Nonparametric
chemical_list: D018956:CD5 Antigens; D003062:Codon; D007143:Immunoglobulin Heavy Chains; D007133:Immunoglobulin Joining Region; D007075:Immunoglobulin M; D007135:Immunoglobulin Variable Region; D011685:Purine Nucleotides; D012694:Serine; D006147:Guanine; D003596:Cytosine; D000225:Adenine