Multiple?sclerosis?or?MS?is?one?of?the?leading?causes?of?neurological?disability?affecting?approximately?2.3?million?people?worldwide.

多發(fā)性硬化癥（MS）是全世界約230萬人罹患神經(jīng)障礙的主要原因之一

In?MS,?the?peak?age?of?onset?is?around?30?years?and?diagnosis?is?about?two?times?more?likely?in?women?than?in?men.

在多發(fā)性硬化癥中，發(fā)病高峰期約為30歲，女性的診斷率是男性的兩倍

The?symptoms?of?MS?may?include?weakness?in?an?arm?or?leg,?sensory?disturbances?such?as?numbness,?tingling?and?pain?problems?with?balance,?and?lack?of?coordination,?fatigue,?cognitive?impairment?and?problems?with?vision?such?as?blurred?or?double?vision.

多發(fā)性硬化癥的癥狀可能包括手臂或腿部無力、感覺障礙，如麻木、刺痛和平衡疼痛問題，以及動(dòng)作協(xié)調(diào)障礙、疲勞、認(rèn)知障礙和視力問題，如視力模糊或復(fù)視

Most?patients?experience?these?symptoms?as?an?initial?series?of?recurrent?deficits?and?remissions,?which?may?be?followed?by?progressive?and?worsening?disability.

最初，大多數(shù)患者的癥狀是一系列復(fù)發(fā)和緩解，隨后可能是進(jìn)行性和惡化性殘疾

In?some?patients,?disability?is?continuously?progressive?from?the?onset?of?disease.

有些患者自疾病發(fā)作，殘疾便不斷進(jìn)展

The?symptoms?of?MS?are?believed?to?result?from?underlying?processes?of?inflammation?and?neuro-degeneration.

多發(fā)性硬化癥的癥狀由炎癥和神經(jīng)退行性變的潛在過程引起的

In?particular,?the?inflammatory?process?causes?destruction?of?myelin?sheaths?and?axons,?leading?in?turn?to?disruptions?of?neurotransmission.

特別需要注意，炎癥過程導(dǎo)致髓鞘和軸突破壞，進(jìn)而導(dǎo)致神經(jīng)傳遞中斷

MS?is?characterized?by?increased?permeability?of?the?blood-brain?barrier,?allowing?immune?cells?such?as?macrophages, T-cells?and?B-cells?to?infiltrate?into?the?CNS.

多發(fā)性硬化癥的特點(diǎn)是血腦屏障的通透性增加，使巨噬細(xì)胞、T細(xì)胞和B細(xì)胞等免疫細(xì)胞滲入中樞神經(jīng)系統(tǒng)

The?traditional?view?of?MS?pathophysiology?holds?that?CD4?positive?T?helper?cells?react?with?components?of?myelin?and?trigger?an?inflammatory?cascade?in?the?CNS,?resulting?in?demyelination?and?axonal?loss.

MS病理生理學(xué)傳統(tǒng)觀點(diǎn)認(rèn)為，CD4+輔助性T細(xì)胞與髓鞘成分反應(yīng)，并觸發(fā)中樞神經(jīng)系統(tǒng)的炎癥級(jí)聯(lián)，導(dǎo)致脫髓鞘和軸突缺失

However, B-cells,?plasma?cells,?and?excess?immunoglobulins?are?known?to?be?present?in?both?lesions?and?cerebrospinal?fluid?of?patients?with?MS.

然而，已知多發(fā)性硬化患者的病變和腦脊液中均存在B細(xì)胞、漿細(xì)胞和過量免疫球蛋白

This?long-standing?recognition?has?suggested?that?B-cells?may?also?play?key?roles?in?the?pathophysiology?of?MS.

這種長期的認(rèn)識(shí)表明，B細(xì)胞也可能在多發(fā)性硬化癥的病理生理學(xué)中發(fā)揮關(guān)鍵作用

In?humans,?the?bone-marrow?functions?as?a?primary?lymphoid?tissue.

在人類中，骨髓作為初級(jí)淋巴組織發(fā)揮作用

B-cells?arise?from?stem?cells?in?the?bone?marrow?where?they?develop?to?form?immature?naive?b-cells.

B細(xì)胞起源于骨髓中的干細(xì)胞，逐漸發(fā)育為不成熟的初始B細(xì)胞

Further,?development?occurs?in?the?spleen?or?lymph?nodes.

此外，也在脾臟或淋巴結(jié)中發(fā)育

At?these?sites,?continuing?maturation?ultimately?gives?rise?to?either?memory?B-cells?or?plasma?cells.

在這些部位，B細(xì)胞持續(xù)成熟，最終產(chǎn)生記憶B細(xì)胞或漿細(xì)胞

Some?b-cells?said?to?be?autoreactive?have?the?capacity?to?recognize?self?antigens.

一些自身激活的B細(xì)胞具有識(shí)別自身抗原的能力

In?healthy?individuals,?the?developmental?process?includes?checkpoints?to?limit?the?production?of?autoreactive?B-cells.

在健康個(gè)體中，發(fā)育過程包括限制B細(xì)胞自身活性產(chǎn)生的檢查點(diǎn)

In?MS,?some?autoreactive?B?cells?are?able?to?bypass?these?checkpoints?and?grow?to?maturity.

在這些成熟的細(xì)胞中，有些細(xì)胞可以繞過這些檢查點(diǎn)生長。

Following?chemical?signals,?it?has?been?shown?that?autoreactive?B-cells?breach?the?blood-brain?barrier?and?traffic?into?the?CNS,?where?they?may?contribute?to?MS?pathobiology?through?different?mechanisms?that?initiate?and?propagate?inflammation.

有研究表明，自體激活的B細(xì)胞在化學(xué)信號(hào)指示下，突破血腦屏障，進(jìn)入中樞神經(jīng)系統(tǒng)，通過不同的機(jī)制，啟動(dòng)和傳播炎癥，促進(jìn)多發(fā)性硬化癥病理學(xué)

Four?possible?mechanisms?of?B-cell?associated?pathophysiology?in?MS?can?be?described.

MS B細(xì)胞相關(guān)病理生理學(xué)有四種可能機(jī)制

Antigen?presentation,?antibody?production,?cytokine?regulation?and?the?formation?of?new?lymphoid?structures?in?the?meninges.

抗原呈遞、抗體產(chǎn)生、細(xì)胞因子調(diào)節(jié)和腦膜內(nèi)新淋巴結(jié)構(gòu)形成

Antigen?presentation?may?play?an?important?role?in?the?immune?response.

抗原呈遞可能在免疫應(yīng)答中起重要作用

B-cells?can?recognize?and?internalize?specific?antigens.

B細(xì)胞能夠識(shí)別并內(nèi)化特定抗原

Intracellular?processing?generates?fragments?of?Antigen,?which?are?subsequently?displayed?on?the?B?cell?surface.

在細(xì)胞內(nèi)加工產(chǎn)生抗原片段，隨后展示在B細(xì)胞表面

Preclinical?models?suggest?that?through?antigen?presentation?and?co-stimulation,?autoreactive?B-cells?in?the?CNS?may?activate?T-cells?for?a?pro-inflammatory?response.

臨床前模型表明，通過抗原呈遞和共刺激，中樞神經(jīng)系統(tǒng)中的自激活B細(xì)胞可激活T細(xì)胞，產(chǎn)生促炎反應(yīng)

B-cells?also?receive?activation?and?proliferation?signals?from?T-cells?during?such?interactions.

在這種相互作用下，B細(xì)胞也從T細(xì)胞接收活化和增殖信號(hào)

Antibodies?may?be?considered?key?effectors?of?humoral?immunity.

抗體可能是體液免疫的關(guān)鍵效應(yīng)物

Preclinical?data?indicate?that?B?cells?including?autoreactive?B?cells?can?differentiate?into?plasma?cells,?producing?antibodies?which?may?bind?to?myelin?sheaths?and?oligodendrocytes.

臨床前數(shù)據(jù)表明，B細(xì)胞包括自身激活的B細(xì)胞可以分化成漿細(xì)胞，產(chǎn)生抗體，可結(jié)合髓鞘和少突膠質(zhì)細(xì)胞

Bound?antibodies?can?induce?the?deposition?of?complement?proteins?on?tissue?surfaces?promoting?injury.

結(jié)合抗體能誘導(dǎo)組織表面補(bǔ)體蛋白沉積，促進(jìn)損傷

Antibodies?may?also?activate?other?immune?cells?such?as?macrophages?or?natural?killer?cells?to?destroy?tissue.

抗體也可以激活其他免疫細(xì)胞，如巨噬細(xì)胞或自然殺傷細(xì)胞，破壞組織

Immune?cells?coordinate?their?activity?through?the?release?of?signaling?molecules?known?as?cytokines.

免疫細(xì)胞通過釋放細(xì)胞因子信號(hào)分子協(xié)調(diào)它們的活性

These?cells?release?a?variety?of?cytokines,?some?of?which?promote?inflammation,?while?others?may?be?protective.

這些細(xì)胞釋放多種細(xì)胞因子，其中一些促進(jìn)炎癥，而另一些可能是保護(hù)性因子

It?has?been?reported?that?B-cells?in?patients?with?MS?tend?to?produce?more?pro-inflammatory?cytokines?and?less?protective?cytokines?compared?with?healthy?controls.

據(jù)報(bào)道，與健康對(duì)照組相比，多發(fā)性硬化癥患者的B細(xì)胞往往產(chǎn)生更多促炎性細(xì)胞因子以及更少的保護(hù)性細(xì)胞因子

In?the?meninges?of?patients?with?progressive?MS, B-cells?may?form?ectopic?lymphoid?structures?or?germinal?centers?through?the?process?of?neo?lymphogenesis.

在進(jìn)行性多發(fā)性硬化患者的腦膜中，B細(xì)胞可能通過新淋巴發(fā)生過程形成異位淋巴結(jié)構(gòu)或生發(fā)中心

These?structures?contain?activated?B?cells?and?follicular?dendritic?cells?in?addition?to?T-cells?and?may?promote?ongoing?T-cell?activation?within?the?brain.

除了T細(xì)胞外，這些結(jié)構(gòu)還包含活化的B細(xì)胞和濾泡樹突狀細(xì)胞，可能促進(jìn)大腦內(nèi)T細(xì)胞持續(xù)激活

Ectopic?lymphoid?structures?may?be?linked?to?microglial?activation,?local?inflammation?and?neuronal?loss?in?the?nearby?cortex.

異位淋巴結(jié)構(gòu)可能與周圍皮質(zhì)的小膠質(zhì)細(xì)胞活化、局部炎癥和神經(jīng)元丟失有關(guān)

In?summary, B-cells?that?target?neural?structures?undergo?abnormal?development,?bypass?immune?tolerance?checkpoints?and?may?play?multiple?roles?in?the?pathophysiology?of?MS.

總之，靶向神經(jīng)結(jié)構(gòu)的B細(xì)胞異常發(fā)育，繞過免疫耐受檢查點(diǎn)，可能在多發(fā)性硬化癥的病理生理學(xué)中發(fā)揮多種作用

B?cells?express?various?surface?receptors?at?different?stages?of?their?development.

B細(xì)胞在其發(fā)育的不同階段表達(dá)不同的表面受體

In?MS,?certain?stages?of?B?cell?maturation?may?be?crucial?to?determining?the?pathogenic?activity?of?B?cells.

在多發(fā)性硬化癥中，B細(xì)胞成熟的某些階段可能是決定B細(xì)胞致病活性的關(guān)鍵

Current?research?is?investigating?whether?the?selective?targeting?of?receptors?expressed?at?specific?stages?of?B?cell?maturation?may?potentially?help?to?eliminate?specific?B-cell?subsets?including?autoreactive?B-cell?subsets?that?are?pathogenic?in?MS.

當(dāng)前研究正在探究選擇性靶向B細(xì)胞成熟的特定階段表達(dá)的受體是否可能有助于消除特定的B細(xì)胞亞群，包括在MS中致病的自身活性B細(xì)胞亞群

筆記：1.MS臨床表現(xiàn)是什么？

2.MS的機(jī)制是什么？

3.MS與B細(xì)胞關(guān)系？