Toll-like receptor agonists synergize with CD40L to induce either proliferation or plasma cell differentiation of mouse B cells.
Toll-like receptor agonists synergize with CD40L to induce either proliferation or plasma cell differentiation of mouse B cells.
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DOI：
10.1371/journal.pone.0025542
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Fournel S
中科院分区：
文献类型：
--
作者：
Boeglin E;Smulski CR;Brun S;Milosevic S;Schneider P;Fournel S
在经典的教条中，病原体被先天免疫细胞感知（通过病原体相关分子模式（PAMP）的识别），先天免疫细胞反过来激活适应性免疫细胞。然而，最近的数据表明，TLR（Toll样受体），最具特征的一类模式识别受体，也由适应性免疫B细胞表达。B细胞主要通过分化为抗体分泌细胞（ASC）在保护性免疫中发挥重要作用。这种分化需要至少两种信号：由B细胞特异性受体（BCR）识别抗原和主要由作用于CD 40的CD 154/CD 40 L提供的T细胞共刺激信号。为了更好地理解先天性和适应性B细胞刺激信号的相互作用，我们评估了TLR、BCR和/或CD 40刺激组合的结果。为此，用合成TLR激动剂、重组小鼠CD 40 L和激动剂抗BCR抗体活化小鼠脾B细胞。如预期的，TLR激动剂诱导小鼠B细胞增殖和活化或分化成ASC。有趣的是，将CD 40信号添加到TLR激动剂中可以刺激B细胞增殖和活化（TLR 3、TLR 4和TLR 9）或分化为ASC（TLR 1/2、TLR 2/6、TLR 4和TLR 7）。向CD 40 L和TLR 3或TLR 9激动剂添加BCR信号并不诱导分化为ASC，这可以解释为进入记忆通路。总之，我们的研究结果表明，PAMPs协同信号从获得性免疫调节B淋巴细胞的命运在体液免疫应答。
In a classical dogma, pathogens are sensed (via recognition of Pathogen Associated Molecular Patterns (PAMPs)) by innate immune cells that in turn activate adaptive immune cells. However, recent data showed that TLRs (Toll Like Receptors), the most characterized class of Pattern Recognition Receptors, are also expressed by adaptive immune B cells. B cells play an important role in protective immunity essentially by differentiating into antibody-secreting cells (ASC). This differentiation requires at least two signals: the recognition of an antigen by the B cell specific receptor (BCR) and a T cell co-stimulatory signal provided mainly by CD154/CD40L acting on CD40. In order to better understand interactions of innate and adaptive B cell stimulatory signals, we evaluated the outcome of combinations of TLRs, BCR and/or CD40 stimulation. For this purpose, mouse spleen B cells were activated with synthetic TLR agonists, recombinant mouse CD40L and agonist anti-BCR antibodies. As expected, TLR agonists induced mouse B cell proliferation and activation or differentiation into ASC. Interestingly, addition of CD40 signal to TLR agonists stimulated either B cell proliferation and activation (TLR3, TLR4, and TLR9) or differentiation into ASC (TLR1/2, TLR2/6, TLR4 and TLR7). Addition of a BCR signal to CD40L and either TLR3 or TLR9 agonists did not induce differentiation into ASC, which could be interpreted as an entrance into the memory pathway. In conclusion, our results suggest that PAMPs synergize with signals from adaptive immunity to regulate B lymphocyte fate during humoral immune response.
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