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TLR Ligation Triggers Somatic Hypermutation in Transitional B Cells Inducing the Generation of IgM Memory B Cells
被引:60
作者:
Aranburu, Alaitz
[1
]
Ceccarelli, Sara
[1
]
Giorda, Ezio
[1
]
Lasorella, Rosa
[2
]
Ballatore, Giovanna
[2
]
Carsetti, Rita
[1
]
机构:
[1] Bambino Gesu Pediat Hosp, Res Ctr, I-00165 Rome, Italy
[2] Osped St Eugenio, I-00144 Rome, Italy
关键词:
DETERMINING REGION 3;
DNA-POLYMERASE ETA;
IMMUNOGLOBULIN GENES;
DIVERSIFICATION;
REPERTOIRE;
MECHANISMS;
AID;
SPECIFICITY;
EXPRESSION;
ANTIBODIES;
D O I:
10.4049/jimmunol.1002722
中图分类号:
R392 [医学免疫学];
Q939.91 [免疫学];
学科分类号:
100102 ;
摘要:
TLR9 activation by unmethylated CpG provides a homeostatic mechanism to maintain B cell memory in the absence of Ag. In this study, we demonstrate that CpG also triggers the generation of somatically mutated memory B cells from immature transitional B cells. In response to CpG, a fraction of transitional B cells proliferates and introduces somatic hypermutations in the H chain V regions. The nonproliferating pool of transitional B cells mostly maintains germline configurations. Mutations are VH specific: VH5 is the least mutated family, whereas VH1 and VH4/6 are the most mutated families. CpG stimulation also results in upregulation of VH5 transcripts in proliferating cells. Therefore, early recognition of bacterial DNA preferentially expands VH5-expressing B cells while inducing somatic hypermutations in other families. The mutation frequency, range, and type of substitutions observed in vitro are comparable to those found in memory B cells from the peripheral blood of Hyper IgM type 1 patients and the spleen of normal infants. The process triggered by TLRs may represent a first step leading to additional diversification of the germline repertoire and to the generation of memory B cells that will further refine their repertoire and specificity in the germinal centers. The Journal of Immunology, 2010, 185: 7293-7301.
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页码:7293 / 7301
页数:9
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