title: Human blood IgM "memory" B cells are circulating splenic marginal zone B cells harboring a prediversified immunoglobulin repertoire.
abstract: The human peripheral B-cell compartment displays a large population of immunoglobulin M-positive, immunoglobulin D-positive CD27(+) (IgM(+)IgD(+)CD27(+)) "memory" B cells carrying a mutated immunoglobulin receptor. By means of phenotypic analysis, complementarity-determining region 3 (CDR3) spectratyping during a T-independent response, and gene-expression profiling of the different blood and splenic B-cell subsets, we show here that blood IgM(+)IgD(+)CD27(+) cells correspond to circulating splenic marginal zone B cells. Furthermore, analysis of this peripheral subset in healthy children younger than 2 years shows that these B cells develop and mutate their immunoglobulin receptor during ontogeny, prior to their differentiation into T-independent antigen-responsive cells. It is therefore proposed that these IgM(+)IgD(+)CD27(+) B cells provide the splenic marginal zone with a diversified and protective preimmune repertoire in charge of the responses against encapsulated bacteria.
authors.affiliation: Institut National de Santé et de la Recherche Médicale U373, Paris, France.
authors.forename: Sandra
authors.initials: S
authors.lastname: Weller
authors.forename: Moritz C
authors.initials: MC
authors.lastname: Braun
authors.forename: Bruce K
authors.initials: BK
authors.lastname: Tan
authors.forename: Andreas
authors.initials: A
authors.lastname: Rosenwald
authors.forename: Corinne
authors.initials: C
authors.lastname: Cordier
authors.forename: Mary Ellen
authors.initials: ME
authors.lastname: Conley
authors.forename: Alessandro
authors.initials: A
authors.lastname: Plebani
authors.forename: Dinakhanta S
authors.initials: DS
authors.lastname: Kumararatne
authors.forename: Damien
authors.initials: D
authors.lastname: Bonnet
authors.forename: Olivier
authors.initials: O
authors.lastname: Tournilhac
authors.forename: Gil
authors.initials: G
authors.lastname: Tchernia
authors.forename: Birte
authors.initials: B
authors.lastname: Steiniger
authors.forename: Louis M
authors.initials: LM
authors.lastname: Staudt
authors.forename: Jean-Laurent
authors.initials: JL
authors.lastname: Casanova
authors.forename: Claude-Agnès
authors.initials: CA
authors.lastname: Reynaud
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Weill
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001327:Autoimmune Diseases / Q000209:etiology / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D001775:Blood Circulation; D002648:Child; D002675:Child, Preschool; D022801:Complementarity Determining Regions / Q000032:analysis; D020869:Gene Expression Profiling; D015322:Gene Rearrangement, B-Lymphocyte; D006801:Humans; D007072:Immunoglobulin D; D007075:Immunoglobulin M; D007156:Immunologic Memory / Q000235:genetics; D016130:Immunophenotyping; D007223:Infant; D008875:Middle Aged; D027041:Somatic Hypermutation, Immunoglobulin; D013154:Spleen / Q000166:cytology*; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7
chemical_list: D022801:Complementarity Determining Regions; D007072:Immunoglobulin D; D007075:Immunoglobulin M; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7