title: CD40-CD40L independent Ig gene hypermutation suggests a second B cell diversification pathway in humans.
abstract: Somatically mutated IgM(+)-only and IgM(+)IgD(+)CD27(+) B lymphocytes comprise approximately 25% of the human peripheral B cell pool. These cells phenotypically resemble class-switched B cells and have therefore been classified as postgerminal center memory B cells. X-linked hyper IgM patients have a genetic defect characterized by a mutation of the CD40L gene. These patients, who do not express a functional CD40 ligand, cannot switch Ig isotypes and do not form germinal centers and memory B cells. We report here that an IgM(+)IgD(+)CD27(+) B cell subset with somatically mutated Ig receptors is generated in these patients, implying that these cells expand and diversify their Ig receptors in the absence of classical cognate T-B collaboration. The presence of this sole subset in the absence of IgM(+)-only and switched CD27(+) memory B cells suggests that it belongs to a separate diversification pathway.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale U373, Faculté de Médecine Necker-Enfants Malades, 156, Rue de Vaugirard, 75730 Paris Cedex 15, France.
authors.forename: S
authors.initials: S
authors.lastname: Weller
authors.forename: A
authors.initials: A
authors.lastname: Faili
authors.forename: C
authors.initials: C
authors.lastname: Garcia
authors.forename: M C
authors.initials: MC
authors.lastname: Braun
authors.forename: F
authors.initials: F
authors.lastname: Le Deist F
authors.forename: G
authors.initials: G
authors.lastname: de Saint Basile G
authors.forename: O
authors.initials: O
authors.lastname: Hermine
authors.forename: A
authors.initials: A
authors.lastname: Fischer
authors.forename: C A
authors.initials: CA
authors.lastname: Reynaud
authors.forename: J C
authors.initials: JC
authors.lastname: Weill
mesh_terms: D000293:Adolescent; D000328:Adult; D017398:Alternative Splicing; D016175:B-Lymphocyte Subsets / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D019013:CD40 Antigens / Q000235:genetics* / Q000276:immunology; D023201:CD40 Ligand / Q000235:genetics* / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D018388:Codon, Terminator; D005312:Fetal Blood / Q000276:immunology; D015321:Gene Rearrangement; D005803:Genes, Immunoglobulin; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood; D007072:Immunoglobulin D / Q000235:genetics; D007074:Immunoglobulin G / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood / Q000235:genetics*; D007153:Immunologic Deficiency Syndromes / Q000097:blood / Q000235:genetics* / Q000276:immunology; D007231:Infant, Newborn; D009154:Mutation; D012016:Reference Values; D017384:Sequence Deletion
chemical_list: D019013:CD40 Antigens; D018388:Codon, Terminator; D007070:Immunoglobulin A; D007072:Immunoglobulin D; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D023201:CD40 Ligand