ZBTB32 restrains antibody responses to murine cytomegalovirus infections, but not other repetitive challenges
ZBTB32 restrains antibody responses to murine cytomegalovirus infections, but not other repetitive challenges
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DOI：
10.1038/s41598-019-51860-z
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发表时间：
2019-10-24
影响因子：
4.6
通讯作者：
Bhattacharya, Deepta
中科院分区：
文献类型：
--
作者：
Jash, Arijita;Zhou, You W.;Bhattacharya, Deepta
ZBTB 32是一种转录因子，由记忆B细胞亚群高度表达，并抑制针对半抗原-蛋白质缀合物的回忆应答的幅度和持续时间。为了定义ZBTB 32作用的生理环境，我们评估了Zbtb 32（-/-）小鼠或骨髓嵌合体对一组慢性和急性挑战的反应。建立了混合骨髓嵌合体，其中所有B细胞均来源于Zbtb 32（-/-）小鼠或对照同窝仔。尽管病毒载量相似，但用鼠巨细胞病毒慢性感染Zbtb 32（-/-）嵌合体在感染后第9周导致抗原特异性IgG 2b水平相对于对照高出近20倍。相比之下，肠道中的伊加反应和特异性，其中记忆B细胞被肠道细菌反复刺激，在Zbtb 32（-/-）小鼠和对照同窝小鼠之间相似。最后，感染和异源加强疫苗接种模型显示ZBTB 32在抑制针对流感病毒的初级或回忆抗体应答中没有作用。因此，ZBTB 32不限制对许多生理急性挑战的回忆反应，但在周期性地接合记忆B细胞的慢性病毒感染期间限制抗体水平。这种限制可能会选择性地阻止对慢性感染的回忆反应逐渐压倒其他抗体特异性。
ZBTB32 is a transcription factor that is highly expressed by a subset of memory B cells and restrains the magnitude and duration of recall responses against hapten-protein conjugates. To define physiological contexts in which ZBTB32 acts, we assessed responses by Zbtb32(-/-) mice or bone marrow chimeras against a panel of chronic and acute challenges. Mixed bone marrow chimeras were established in which all B cells were derived from either Zbtb32(-/-) mice or control littermates. Chronic infection of Zbtb32(-/-) chimeras with murine cytomegalovirus led to nearly 20-fold higher antigen-specific IgG2b levels relative to controls by week 9 post-infection, despite similar viral loads. In contrast, IgA responses and specificities in the intestine, where memory B cells are repeatedly stimulated by commensal bacteria, were similar between Zbtb32(-/-) mice and control littermates. Finally, an infection and heterologous booster vaccination model revealed no role for ZBTB32 in restraining primary or recall antibody responses against influenza viruses. Thus, ZBTB32 does not limit recall responses to a number of physiological acute challenges, but does restrict antibody levels during chronic viral infections that periodically engage memory B cells. This restriction might selectively prevent recall responses against chronic infections from progressively overwhelming other antibody specificities.