Toll-like receptor 9 antagonizes antibody affinity maturation

被引：51

作者：

Akkaya, Munir ^{[1
]}

Akkaya, Billur ^{[2
]}

Kim, Ann S. ^{[1
]}

Miozzo, Pietro ^{[1
]}

Sohn, Haewon ^{[1
]}

Pena, Mirna ^{[1
]}

Roesler, Alexander S. ^{[1
]}

Theall, Brandon P. ^{[1
]}

Henke, Travis ^{[1
]}

Kabat, Juraj ^{[3
]}

Lu, Jinghua ^{[1
]}

Dorward, David W. ^{[4
]}

Dahlstrom, Eric ^{[4
]}

Skinner, Jeff ^{[1
]}

Millers, Louis H. ^{[5
]}

Pierce, Susan K. ^{[1
]}

机构：

[1] NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA

[2] NIAID, Immunol Lab, NIH, Bldg 10, Bethesda, MD 20892 USA

[3] NIAID, Res Technol Branch, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA

[4] NIAID, Res Technol Branch, NIH, Hamilton, MT USA

[5] NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD USA

来源：

NATURE IMMUNOLOGY | 2018年 / 19卷 / 03期

基金：

美国国家卫生研究院;

关键词：

MEMORY B-CELLS; GERMINAL CENTER; RESPONSES; DIFFERENTIATION; PROLIFERATION; LYMPHOCYTES; MEMBRANE; ENERGY;

D O I：

10.1038/s41590-018-0052-z

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Key events in T cell-dependent antibody responses, including affinity maturation, are dependent on the B cell's presentation of antigen to helper T cells at critical checkpoints in germinal-center formation in secondary lymphoid organs. Here we found that signaling via Toll-like receptor 9 (TLR9) blocked the ability of antigen-specific B cells to capture, process and present antigen and to activate antigen-specific helper T cells in vitro. In a mouse model in vivo and in a human clinical trial, the TLR9 agonist CpG enhanced the magnitude of the antibody response to a protein vaccine but failed to promote affinity maturation. Thus, TLR9 signaling might enhance antibody titers at the expense of the ability of B cells to engage in germinal-center events that are highly dependent on B cells' capture and presentation of antigen.

引用

页码：255 / +

页数：18

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