Blood:BAFF和CD4+T细胞,助纣为虐,保护导致免疫性血细胞减少的长寿命的脾内浆细胞的存活

2018-02-01 MedSci MedSci原创

背景:浆细胞(PCs)是终末分化的B细胞,可产生抗体。长寿命的浆细胞(LLPCs)主要存在于骨髓,可存活10年之久。PCs的寿命取决于形成特定存活壁龛的支持性环境,而LLPCs的数量常受壁龛的有限空间的限制。患自身免疫性疾病时,脾脏和受侵犯的组织中可形成的存活壁龛,储存自身反应性的LLPCs。中心点:B细胞消耗诱导的脾脏微环境改变,使浆细胞对BAFF和CD4+ T细胞产生依赖性。联合抗-CD20和

背景:浆细胞(PCs)是终末分化的B细胞,可产生抗体。长寿命的浆细胞(LLPCs)主要存在于骨髓,可存活10年之久。PCs的寿命取决于形成特定存活壁龛的支持性环境,而LLPCs的数量常受壁龛的有限空间的限制。患自身免疫性疾病时,脾脏和受侵犯的组织中可形成的存活壁龛,储存自身反应性的LLPCs。

中心点:

B细胞消耗诱导的脾脏微环境改变,使浆细胞对BAFF和CD4+ T细胞产生依赖性。

联合抗-CD20和抗-BAFF,可减少脾脏浆细胞的数量,为治疗抗体介导的血细胞减少提供新的治疗角度。

摘要:

既往数据表明,B细胞耗竭疗法可减少自身免疫性血细胞减少的患者脾脏内自身免疫性的LLPCs。但其潜在的作用机制尚不明确,现有研究人员利用AID-CreERT2-EYFP小鼠模型来追踪参与免疫反应的浆细胞(PCs)。在单细胞水平进行多重PCR发现只有一小部分的脾脏PCs是长寿命的,而且,经过抗CD20抗体治疗后,脾脏PCs更加成熟,接近骨髓PCs。上述结果表明除了选择的过程外,B细胞耗竭所诱导的成熟也可促进PCs获得长寿。

抗CD20联合抗BAFF或抗CD4抗体处理可明显减少脾脏的浆细胞,因此研究人员推断BAFF和CD4+T细胞在浆细胞壁龛中发挥重要作用。而且,研究人员在系统性红斑狼疮(免疫性疾病)的NZB/W模型中观察到相似的结果。脾脏浆细胞壁龛的可溶性和细胞性组分的不同作用证明LLPC表达谱不是细胞所固有的,而是很大程度上依赖于脾脏微环境所提供的信号,提示在B细胞耗竭时对这些成分进行干扰或许可提高自身免疫性血细胞减少的治疗反应率。

原始出处:

Lan-Huong Thai,et al.BAFF and CD4+ T cells are major survival factors for long-lived splenic plasma cells in a B-cell-depletion context.Blood  2018  :blood-2017-06-789578;  doi: https://doi.org/10.1182/blood-2017-06-789578

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    2018-11-30 徐岩
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  4. 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encryptionId=5082432634, topicName=CD4+)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=4c1624305102, createdName=xuyu, createdTime=Tue Jul 17 06:21:00 CST 2018, time=2018-07-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1864228, encodeId=209918642286c, content=<a href='/topic/show?id=f930432538' target=_blank style='color:#2F92EE;'>#CD4#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=35, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4325, encryptionId=f930432538, topicName=CD4)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=b09892, createdName=qidongfanjian, createdTime=Fri Mar 09 17:21:00 CST 2018, time=2018-03-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=287987, encodeId=b09e28e987ac, content=学习了.谢谢分享!, beContent=null, objectType=article, channel=null, level=null, likeNumber=61, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cdnapi.center.medsci.cn/medsci/head/2019/12/23/2f51002e1349ccda5be11c1eea1e1e60.jpg, createdBy=a22097948, createdName=天地飞扬, createdTime=Wed Feb 14 22:51:38 CST 2018, time=2018-02-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1466604, encodeId=cd591466604c1, content=<a href='/topic/show?id=8d3e65434d4' target=_blank style='color:#2F92EE;'>#浆细胞#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=43, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=65434, encryptionId=8d3e65434d4, topicName=浆细胞)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=181c6846356, createdName=huangshifeng, createdTime=Sat Feb 03 01:21:00 CST 2018, time=2018-02-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1500969, encodeId=9d18150096936, content=<a href='/topic/show?id=04794329fc' target=_blank style='color:#2F92EE;'>#CD4+T细胞#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=52, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4329, encryptionId=04794329fc, topicName=CD4+T细胞)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=cd149483945, createdName=海豹, createdTime=Sat Feb 03 01:21:00 CST 2018, time=2018-02-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=284220, encodeId=2e6928422001, content=不确定性太多.需要努力学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=43, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/mONcle9pic3zMoyicyo6ia9f4IuLQAwZoxD6Hx4ibd5CMcOCYhStY6oDibbKK6O2X8iaicldO5ib8j1iapOIobIKCGiczU2A/0, createdBy=56251941490, createdName=虈亣靌, createdTime=Thu Feb 01 19:15:47 CST 2018, time=2018-02-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=284140, encodeId=3ddc284140d4, content=学习谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=66, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/mStl88fu4Nd44v3xHnnictn9UpctwtH62EPQ59TMdI9lnqHMgQ16nH7GmGCfpzicsHgjibYVk6vwSpXrC86gMibRkoaIzf5HwSz7/0, createdBy=78cc1691107, createdName=龙胆草, createdTime=Thu Feb 01 10:35:17 CST 2018, time=2018-02-01, status=1, ipAttribution=)]
    2018-07-17 xuyu
  5. 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topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cdnapi.center.medsci.cn/medsci/head/2019/12/23/2f51002e1349ccda5be11c1eea1e1e60.jpg, createdBy=a22097948, createdName=天地飞扬, createdTime=Wed Feb 14 22:51:38 CST 2018, time=2018-02-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1466604, encodeId=cd591466604c1, content=<a href='/topic/show?id=8d3e65434d4' target=_blank style='color:#2F92EE;'>#浆细胞#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=43, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=65434, encryptionId=8d3e65434d4, topicName=浆细胞)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=181c6846356, createdName=huangshifeng, createdTime=Sat Feb 03 01:21:00 CST 2018, time=2018-02-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1500969, encodeId=9d18150096936, content=<a href='/topic/show?id=04794329fc' target=_blank style='color:#2F92EE;'>#CD4+T细胞#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=52, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4329, encryptionId=04794329fc, topicName=CD4+T细胞)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=cd149483945, createdName=海豹, createdTime=Sat Feb 03 01:21:00 CST 2018, time=2018-02-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=284220, encodeId=2e6928422001, content=不确定性太多.需要努力学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=43, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/mONcle9pic3zMoyicyo6ia9f4IuLQAwZoxD6Hx4ibd5CMcOCYhStY6oDibbKK6O2X8iaicldO5ib8j1iapOIobIKCGiczU2A/0, createdBy=56251941490, createdName=虈亣靌, createdTime=Thu Feb 01 19:15:47 CST 2018, time=2018-02-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=284140, encodeId=3ddc284140d4, content=学习谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=66, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/mStl88fu4Nd44v3xHnnictn9UpctwtH62EPQ59TMdI9lnqHMgQ16nH7GmGCfpzicsHgjibYVk6vwSpXrC86gMibRkoaIzf5HwSz7/0, createdBy=78cc1691107, createdName=龙胆草, createdTime=Thu Feb 01 10:35:17 CST 2018, time=2018-02-01, status=1, ipAttribution=)]
    2018-03-09 qidongfanjian
  6. 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topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cdnapi.center.medsci.cn/medsci/head/2019/12/23/2f51002e1349ccda5be11c1eea1e1e60.jpg, createdBy=a22097948, createdName=天地飞扬, createdTime=Wed Feb 14 22:51:38 CST 2018, time=2018-02-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1466604, encodeId=cd591466604c1, content=<a href='/topic/show?id=8d3e65434d4' target=_blank style='color:#2F92EE;'>#浆细胞#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=43, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=65434, encryptionId=8d3e65434d4, topicName=浆细胞)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=181c6846356, createdName=huangshifeng, createdTime=Sat Feb 03 01:21:00 CST 2018, time=2018-02-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1500969, encodeId=9d18150096936, content=<a href='/topic/show?id=04794329fc' target=_blank style='color:#2F92EE;'>#CD4+T细胞#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=52, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4329, encryptionId=04794329fc, topicName=CD4+T细胞)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=cd149483945, createdName=海豹, createdTime=Sat Feb 03 01:21:00 CST 2018, time=2018-02-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=284220, encodeId=2e6928422001, content=不确定性太多.需要努力学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=43, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/mONcle9pic3zMoyicyo6ia9f4IuLQAwZoxD6Hx4ibd5CMcOCYhStY6oDibbKK6O2X8iaicldO5ib8j1iapOIobIKCGiczU2A/0, createdBy=56251941490, createdName=虈亣靌, createdTime=Thu Feb 01 19:15:47 CST 2018, time=2018-02-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=284140, encodeId=3ddc284140d4, content=学习谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=66, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/mStl88fu4Nd44v3xHnnictn9UpctwtH62EPQ59TMdI9lnqHMgQ16nH7GmGCfpzicsHgjibYVk6vwSpXrC86gMibRkoaIzf5HwSz7/0, createdBy=78cc1691107, createdName=龙胆草, createdTime=Thu Feb 01 10:35:17 CST 2018, time=2018-02-01, status=1, ipAttribution=)]
    2018-02-14 天地飞扬

    学习了.谢谢分享!

    0

  7. 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topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cdnapi.center.medsci.cn/medsci/head/2019/12/23/2f51002e1349ccda5be11c1eea1e1e60.jpg, createdBy=a22097948, createdName=天地飞扬, createdTime=Wed Feb 14 22:51:38 CST 2018, time=2018-02-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1466604, encodeId=cd591466604c1, content=<a href='/topic/show?id=8d3e65434d4' target=_blank style='color:#2F92EE;'>#浆细胞#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=43, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=65434, encryptionId=8d3e65434d4, topicName=浆细胞)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=181c6846356, createdName=huangshifeng, createdTime=Sat Feb 03 01:21:00 CST 2018, time=2018-02-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1500969, encodeId=9d18150096936, content=<a href='/topic/show?id=04794329fc' target=_blank 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GetPortalCommentsPageByObjectIdResponse(id=284140, encodeId=3ddc284140d4, content=学习谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=66, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/mStl88fu4Nd44v3xHnnictn9UpctwtH62EPQ59TMdI9lnqHMgQ16nH7GmGCfpzicsHgjibYVk6vwSpXrC86gMibRkoaIzf5HwSz7/0, createdBy=78cc1691107, createdName=龙胆草, createdTime=Thu Feb 01 10:35:17 CST 2018, time=2018-02-01, status=1, ipAttribution=)]
  8. 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style='color:#2F92EE;'>#CD4+T细胞#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=52, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4329, encryptionId=04794329fc, topicName=CD4+T细胞)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=cd149483945, createdName=海豹, createdTime=Sat Feb 03 01:21:00 CST 2018, time=2018-02-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=284220, encodeId=2e6928422001, content=不确定性太多.需要努力学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=43, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/mONcle9pic3zMoyicyo6ia9f4IuLQAwZoxD6Hx4ibd5CMcOCYhStY6oDibbKK6O2X8iaicldO5ib8j1iapOIobIKCGiczU2A/0, createdBy=56251941490, createdName=虈亣靌, createdTime=Thu Feb 01 19:15:47 CST 2018, time=2018-02-01, status=1, ipAttribution=), 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  9. [GetPortalCommentsPageByObjectIdResponse(id=1971705, encodeId=6c9c19e170551, content=<a href='/topic/show?id=3033898847f' target=_blank style='color:#2F92EE;'>#血细胞减少#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=51, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=89884, encryptionId=3033898847f, topicName=血细胞减少)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=aad0444, createdName=cmsvly, createdTime=Sun Aug 19 18:21:00 CST 2018, time=2018-08-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1652572, encodeId=548616525e243, content=<a href='/topic/show?id=ca9831e3f4' target=_blank style='color:#2F92EE;'>#BAFF#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=44, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=3173, encryptionId=ca9831e3f4, topicName=BAFF)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=62ca24296368, 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style='color:#2F92EE;'>#CD4+T细胞#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=52, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4329, encryptionId=04794329fc, topicName=CD4+T细胞)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=cd149483945, createdName=海豹, createdTime=Sat Feb 03 01:21:00 CST 2018, time=2018-02-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=284220, encodeId=2e6928422001, content=不确定性太多.需要努力学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=43, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/mONcle9pic3zMoyicyo6ia9f4IuLQAwZoxD6Hx4ibd5CMcOCYhStY6oDibbKK6O2X8iaicldO5ib8j1iapOIobIKCGiczU2A/0, createdBy=56251941490, createdName=虈亣靌, createdTime=Thu Feb 01 19:15:47 CST 2018, time=2018-02-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=284140, encodeId=3ddc284140d4, content=学习谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=66, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/mStl88fu4Nd44v3xHnnictn9UpctwtH62EPQ59TMdI9lnqHMgQ16nH7GmGCfpzicsHgjibYVk6vwSpXrC86gMibRkoaIzf5HwSz7/0, createdBy=78cc1691107, createdName=龙胆草, createdTime=Thu Feb 01 10:35:17 CST 2018, time=2018-02-01, status=1, ipAttribution=)]
    2018-02-01 虈亣靌

    不确定性太多.需要努力学习

    0

  10. 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GetPortalCommentsPageByObjectIdResponse(id=284140, encodeId=3ddc284140d4, content=学习谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=66, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/mStl88fu4Nd44v3xHnnictn9UpctwtH62EPQ59TMdI9lnqHMgQ16nH7GmGCfpzicsHgjibYVk6vwSpXrC86gMibRkoaIzf5HwSz7/0, createdBy=78cc1691107, createdName=龙胆草, createdTime=Thu Feb 01 10:35:17 CST 2018, time=2018-02-01, status=1, ipAttribution=)]
    2018-02-01 龙胆草

    学习谢谢分享

    0

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在7月4日的第八届中国肿瘤内科大会会上,第二军医大学长征医院血液科的侯健教授介绍了多发性骨髓瘤的生物学特性与靶向治疗。   骨髓瘤细胞的生物学特性 多发性骨髓瘤是发生在浆细胞的恶性肿瘤。浆细胞发育、分化过程中产生的分子与细胞遗传学损伤对于MM的发生起到关键的作用。骨髓瘤细胞产生的M蛋白及其代谢途径也是骨髓瘤治疗的重要靶点。骨髓瘤细胞还通过与骨髓微环境相互作用促进瘤细胞的增殖、阻止其凋