Human blood IgM "memory" B cells are circulating splenic marginal zone B cells harboring a prediversified immunoglobulin repertoire.
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.
Weller
Sandra
S
Institut National de Santé et de la Recherche Médicale U373, Paris, France.
Braun
Moritz C
MC
Tan
Bruce K
BK
Rosenwald
Andreas
A
Cordier
Corinne
C
Conley
Mary Ellen
ME
Plebani
Alessandro
A
Kumararatne
Dinakhanta S
DS
Bonnet
Damien
D
Tournilhac
Olivier
O
Tchernia
Gil
G
Steiniger
Birte
B
Staudt
Louis M
LM
Casanova
Jean-Laurent
JL
Reynaud
Claude-Agnès
CA
Weill
Jean-Claude
JC
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
D022801:Complementarity Determining Regions; D007072:Immunoglobulin D; D007075:Immunoglobulin M; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7