Re-utilization of germinal centers in multiple Peyer's patches results in highly synchronized, oligoclonal, and affinity-matured gut IgA responses

被引：77

作者：

Bergqvist, P. ^{[1
]}

Stensson, A. ^{[1
]}

Hazanov, L. ^{[2
]}

Holmberg, A. ^{[1
]}

Mattsson, J. ^{[1
]}

Mehr, R. ^{[2
]}

Bemark, M. ^{[1
]}

Lycke, N. Y. ^{[1
]}

机构：

[1] Univ Gothenburg, Inst Biomed, Mucosal Immunobiol & Vaccine Res Ctr MIVAC, Dept Microbiol & Immunol, Gothenburg, Sweden

[2] Bar Ilan Univ, Mina & Everard Goodman Fac Life Sci, Ramat Gan, Israel

来源：

MUCOSAL IMMUNOLOGY | 2013年 / 6卷 / 01期

基金：

以色列科学基金会; 瑞典研究理事会;

关键词：

LYMPHOID FOLLICLE FORMATION; CLASS SWITCH RECOMBINATION; LYMPHOTOXIN-BETA-RECEPTOR; SUFFICIENT B-LYMPHOCYTES; PRIMARY IMMUNE-RESPONSE; CHOLERA-TOXIN; IMMUNOGLOBULIN-A; DENDRITIC CELLS; LAMINA PROPRIA; IN-SITU;

D O I：

10.1038/mi.2012.56

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Whereas gut IgA responses to the microbiota may be multi-centered and diverse, little is known about IgA responses to T-cell-dependent antigens following oral immunizations. Using a novel approach, gut IgA responses to oral hapten (4-hydroxy-3-nitrophenyl) acetyl-cholera toxin (NP-CT) conjugates were followed at the cellular and molecular level. Surprisingly, these responses were highly synchronized, strongly oligoclonal, and dominated by affinity matured cells. Extensive lineage trees revealed clonal relationships between NP-specific IgA cells in gut inductive and effector sites, suggesting expansion of the same B-cell clone in multiple Peyer's patches (PPs). Adoptive transfer experiments showed that this was achieved through re-utilization of already existing germinal centers (GCs) in multiple PPs by previously activated GC GL7(+) B cells, provided oral NP-CT was given before cell transfer. Taken together, these results explain why repeated oral immunizations are mandatory for an effective oral vaccine.

引用

页码：122 / 135

页数：14