Establishment of isotype-switched, antigen-specific B cells in multiple mucosal tissues using non-mucosal immunization.
Establishment of isotype-switched, antigen-specific B cells in multiple mucosal tissues using non-mucosal immunization.
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DOI：
10.1038/s41541-023-00677-z
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发表时间：
2023-05-31
期刊：
影响因子：
9.2
通讯作者：
中科院分区：
文献类型：
--
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虽然大多数病原体通过粘膜表面感染人体，但很少有注射疫苗可以特异性地将免疫细胞靶向到这些组织中，在这些组织中它们的效应功能是最理想的。我们之前已经证明，某些佐剂可以编程疫苗特异性辅助性T细胞迁移到肠道，即使疫苗是非粘膜递送。目前尚不清楚这是否适用于抗原特异性B细胞反应。本研究表明，单次皮内接种佐剂双突变热不稳定毒素（dmLT）可诱导强大的内源性、疫苗特异性、同型转换的B细胞应答。当皮下注射疫苗时，我们在大肠、Peyer’s补丁和肺部的固有层中检测到非循环疫苗特异性B细胞反应。与TLR9配体佐剂CpG相比，只有dmLT能够在这些粘膜组织中驱动同型转换的驻留B细胞的建立，即使在dmLT佐剂疫苗非粘膜注射时也是如此。此外，我们发现转录因子Batf3对这些B细胞的完整生发中心反应、同型转换和Peyer 's patch迁移很重要。总的来说，这些数据表明特异性佐剂可以促进粘膜归巢，并在粘膜组织中建立活化的抗原特异性B细胞，即使这些佐剂通过非粘膜途径递送。这些发现可能从根本上改变未来疫苗的配方和交付方式。
Although most pathogens infect the human body via mucosal surfaces, very few injectable vaccines can specifically target immune cells to these tissues where their effector functions would be most desirable. We have previously shown that certain adjuvants can program vaccine-specific helper T cells to migrate to the gut, even when the vaccine is delivered non-mucosally. It is not known whether this is true for antigen-specific B cell responses. Here we show that a single intradermal vaccination with the adjuvant double mutant heat-labile toxin (dmLT) induces a robust endogenous, vaccine-specific, isotype-switched B cell response. When the vaccine was intradermally boosted, we detected non-circulating vaccine-specific B cell responses in the lamina propria of the large intestines, Peyer’s patches, and lungs. When compared to the TLR9 ligand adjuvant CpG, only dmLT was able to drive the establishment of isotype-switched resident B cells in these mucosal tissues, even when the dmLT-adjuvanted vaccine was administered non-mucosally. Further, we found that the transcription factor Batf3 was important for the full germinal center reaction, isotype switching, and Peyer’s patch migration of these B cells. Collectively, these data indicate that specific adjuvants can promote mucosal homing and the establishment of activated, antigen-specific B cells in mucosal tissues, even when these adjuvants are delivered by a non-mucosal route. These findings could fundamentally change the way future vaccines are formulated and delivered.
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DOI：
10.4049/jimmunol.1601775
发表时间：
2017-07-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Boyaka PN
通讯作者：
Boyaka PN
影响因子：
100.3
作者：
Chen, Kang;Magri, Giuliana;Grasset, Emilie K.;Cerutti, Andrea
通讯作者：
Cerutti, Andrea
DOI：
10.1084/jem.184.5.1879
发表时间：
1996-11-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Gallichan WS;Rosenthal KL
通讯作者：
Rosenthal KL
影响因子：
6.4
作者：
Aviles, Jenna;Bello, Alexander;Kobinger, Gary
通讯作者：
Kobinger, Gary
DOI：
10.1073/pnas.95.4.1709
发表时间：
1998-02-17
影响因子：
11.1
作者：
Belyakov, IM;Derby, MA;Berzofsky, JA
通讯作者：
Berzofsky, JA