Nature:新发现!机体感染病原体之前 肠道微生物或会塑造机体多种抗体的产生!

2020-08-11 DAVID K 细胞

肠道内生存的良性微生物的数量与体内的细胞数量大致相同,大部分细菌都会停留在肠道内而无法穿透机体组织,但不幸的是,肠道菌群的有些渗透过程是无法避免的。

B细胞是一种能发育产生抗体的白细胞,其所产生的抗体/免疫球蛋白能与有害的外来颗粒(病毒或致病菌等)结合并阻断其对宿主的入侵及对机体细胞的感染,每一个B细胞都会携带单一的B细胞受体(BCR)其能帮助确定所结合的外源性物质,这就好像每个锁子能接受一个不同的钥匙一样。机体中拥有数百万个携带不同受体的B细胞,B细胞的巨大多样性源于编码受体基因的重新排列,所以每个B细胞表面的受体都会略有不同,从而就会使其能够识别数十亿种不同的有害性分子;此外,肠道微生物还能诱发这些B细胞群体的扩张和抗体的产生,但直到现在,研究人员并不清楚是否这是一个随机的过程,还是肠道微生物的分子自身影响了结果。

近日,一项刊登在国际杂志Nature上的研究报告中,来自伯尔尼大学等机构的科学家们通过研究分析了该系统中编码抗体产生的数十亿个基因的表达情况,该系统能让科学家们了解基因对单个良性肠道微生物的反应。肠道内生存的良性微生物的数量与体内的细胞数量大致相同,大部分细菌都会停留在肠道内而无法穿透机体组织,但不幸的是,肠道菌群的有些渗透过程是无法避免的,因为肠道仅仅拥有一层细胞,其能将我们吸收食物营养所需要的血管与血管内部分开/隔绝开。

研究者Limenitakis表示,我们能利用一种专门设计的计算机程序来处理数百万个遗传序列,这些遗传序列能比较来自B细胞中抗体库,而其依赖于微生物是否停留在肠道内还是会抵达血液中,在这两种情况下,抗体库就会发生改变,但其改变的方式取决于暴露所发生的方式。有意思的是,这是可以进行预测的,因为其取决于研究者所关注的微生物及其在体内的精确位置,这就提示,肠道微生物或会在机体遭遇严重感染前指导抗体的形成,而其这个过程或许并不是随机的。

与血液中的抗体(IgM和IgG)相比,肠道内壁中的抗体(IgA)有着不同的种类,利用强大的遗传分析技术,研究人员发现,肠道中所产生的不同抗体的范围或许远远小于机体中枢组织中所产生的抗体,这就意味着,一旦微生物进入体内,免疫系统就会有很多可能性来中和并消灭这些微生物,而肠道中的抗体则主要会对其任何时候所见到的细菌分子进行识别并结合。

研究者表示,哺乳动物在其生命周期中会面临多种不同微生物的挑战,因此,重要的是,我们就要知道,一旦抗体库发生改变,其如何被一种特定的微生物所塑造;随后研究人员通过检测不同位点相同微生物所发生的改变或两种微生物相继发生的改变来回答这个问题。虽然肠道微生物并不会直接产生多种不同的抗体,但如果其进入血液就会促进中枢免疫组织变得敏感进而产生抗体,当第二种微生物出现时,相当有限的肠道抗体反应就会发生改变从而适应这种微生物,这就好比是门上的锁子一样,这或许与微生物进入血液达到中枢机体组织时的情况不同,当第二组抗体产生时或许就不会影响原始微生物所产生的第一反应(就好比安装了另外一把锁,这样就能利用不同的钥匙打开门一样),研究者指出,中枢机体组织有能力记住一系列不同的微生物菌群,并能避免败血症所造成的损伤,在不同的机体区室中,不同的B细胞免疫策略对于维持与微生物“旅客”之间的和平共处是非常重要的。

最后研究者Li表示,本文研究结果不仅首次揭示了肠道微生物的组成,而且还发现,机体暴露于某些共生微生物成员的时间和序列或许主要发生在早期的第一次“定植”浪潮中,而这对于所产生的B细胞受体库以及机体对病原体的免疫力或许会产生一定的影响。

原始出处:

Hai Li, Julien P Limenitakis, Victor Greiff,et al.Mucosal or systemic microbiota exposures shape the B cell repertoire.Nature. 2020 Aug 5. doi: 10.1038/s41586-020-2564-6.

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    2020-09-25 liye789132251
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    2021-06-15 wjcjjian
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    2020-08-13 xue8605
  5. [GetPortalCommentsPageByObjectIdResponse(id=1921290, encodeId=bddc192129004, content=<a href='/topic/show?id=6bfa58133ef' target=_blank style='color:#2F92EE;'>#新发现#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=36, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=58133, encryptionId=6bfa58133ef, topicName=新发现)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=644e456, createdName=vera_1203, createdTime=Fri Feb 05 06:18:43 CST 2021, time=2021-02-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1884568, encodeId=3d3b1884568f3, content=<a href='/topic/show?id=3b2112532d8' target=_blank style='color:#2F92EE;'>#Nat#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=31, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12532, encryptionId=3b2112532d8, topicName=Nat)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=2e6f107, createdName=liye789132251, createdTime=Fri Sep 25 13:18:43 CST 2020, time=2020-09-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1825190, encodeId=2156182519008, content=<a href='/topic/show?id=702a5065860' target=_blank style='color:#2F92EE;'>#微生物#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=50658, encryptionId=702a5065860, topicName=微生物)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=0b7c20, createdName=wjcjjian, createdTime=Tue Jun 15 19:18:43 CST 2021, time=2021-06-15, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1510666, encodeId=a82c1510666b6, content=<a href='/topic/show?id=2efbe0807b1' target=_blank style='color:#2F92EE;'>#病原体#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=35, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=70807, encryptionId=2efbe0807b1, topicName=病原体)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f6c210226313, createdName=xue8605, createdTime=Thu Aug 13 02:18:43 CST 2020, time=2020-08-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1604342, encodeId=eb5f160434291, content=<a href='/topic/show?id=71b95335396' target=_blank style='color:#2F92EE;'>#感染病#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=40, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=53353, encryptionId=71b95335396, topicName=感染病)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=337119178396, createdName=xugc, createdTime=Thu Aug 13 02:18:43 CST 2020, time=2020-08-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=807460, encodeId=950f80e460f3, content=阅读, beContent=null, objectType=article, channel=null, level=null, likeNumber=87, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c3282551952, createdName=12543f43m99暂无昵称, createdTime=Tue Aug 11 11:37:28 CST 2020, time=2020-08-11, status=1, ipAttribution=)]
    2020-08-13 xugc
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    2020-08-11 12543f43m99暂无昵称

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