Secondary Immunization Generates Clonally Related Antigen-Specific Plasma Cells and Memory B Cells

被引:67
作者
Froelich, Daniela [1 ,2 ]
Giesecke, Claudia [1 ,2 ]
Mei, Henrik E. [1 ,2 ]
Reiter, Karin [1 ,2 ]
Daridon, Capucine [1 ,2 ]
Lipsky, Peter E. [3 ]
Doerner, Thomas [1 ,2 ]
机构
[1] Charite, Dept Med Rheumatol & Clin Immunol, D-10117 Berlin, Germany
[2] Deutsch Rheumaforschungszentrum Berlin, Berlin, Germany
[3] NIAMSD, NIH, Bethesda, MD 20892 USA
关键词
GENE REPERTOIRE; SOMATIC HYPERMUTATION; CHEMOKINE RECEPTOR; IMMUNE-RESPONSE; INFLUENZA-VIRUS; CHAIN; AFFINITY; BLOOD; DIFFERENTIATION; EXPRESSION;
D O I
10.4049/jimmunol.1000911
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Rechallenge with T cell-dependent Ags induces memory B cells to re-enter germinal centers (GCs) and undergo further expansion and differentiation into plasma cells (PCs) and secondary memory B cells. It is currently not known whether the expanded population of memory B cells and PCs generated in secondary GCs are clonally related, nor has the extent of proliferation and somatic hypermutation of their precursors been delineated. In this study, after secondary tetanus toxoid (TT) immunization, TT-specific PCs increased 17- to 80-fold on days 6-7, whereas TT-specific memory B cells peaked (delayed) on day 14 with a 2- to 22-fold increase. Molecular analyses of V(H)DJ(H) rearrangements of individual cells revealed no major differences of gene usage and CDR3 length between TT-specific PCs and memory B cells, and both contained extensive evidence of somatic hypermutation with a pattern consistent with GC reactions. This analysis identified clonally related TT-specific memory B cells and PCs. Within clusters of clonally related cells, sequences shared a number of mutations but also could contain additional base pair changes. The data indicate that although following secondary immunization PCs can derive from memory B cells without further somatic hypermutation, in some circumstances, likely within GC reactions, asymmetric mutation can occur. These results suggest that after the fate decision to differentiate into secondary memory B cells or PCs, some committed precursors continue to proliferate and mutate their V-H genes. The Journal of Immunology, 2010, 185: 3103-3110.
引用
收藏
页码:3103 / 3110
页数:8
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