小柯机器人

澳大利亚莫纳什大学David M. Tarlinton和Marcus James Robinson共同合作，近期取得重要工作进展。他们研究发现内在决定的周转是浆细胞寿命广泛异质性的基础。相关研究成果2023年5月9日在线发表于《免疫》杂志上。

据介绍，由分泌抗体的浆细胞（ASC）产生的抗体是多种形式持久免疫的基础。

研究人员使用报告基因对ASC进行时间标记，研究了调节ASC周转和持久性的机制。这种方法揭示了ASC的寿命是异质的，并且是连续的，只有一小部分存活了60天以上。ASC超过60天的寿命与同种型无关，但与逐渐发展的表型相关，并最终与潜在的“长寿”ASC（LL ASC）富集转录程序相关。虽然LL ASC和其他ASC之间的一些差异似乎是随着年龄的增长而获得的，但一些年轻的ASC也有其它特征，如高CD138和CD93。周转率不受ASC生产变化的影响，反对将小生境竞争作为周转率的主要驱动因素。

因此，ASC更替是由固有寿命限制决定的，稳态种群动态由生态位空缺而非置换决定。

附：英文原文

Title: Intrinsically determined turnover underlies broad heterogeneity in plasma-cell lifespan

Author: Marcus James Robinson, Zhoujie Ding, Mark R. Dowling, Danika L. Hill, Rosela H. Webster, Craig McKenzie, Catherine Pitt, Kristy O’Donnell, Jesse Mulder, Erica Brodie, Philip D. Hodgkin, Nick C. Wong, Isaak Quast, David M. Tarlinton

Issue&Volume: 2023-05-09

Abstract: Antibodies produced by antibody-secreting plasma cells (ASCs) underlie multiple formsof long-lasting immunity. Here we examined the mechanisms regulating ASC turnoverand persistence using a genetic reporter to time-stamp ASCs. This approach revealedASC lifespans as heterogeneous and falling on a continuum, with only a small fractionsurviving for >60 days. ASC longevity past 60 days was independent of isotype butcorrelated with a phenotype that developed progressively and ultimately associatedwith an underlying "long-lived" ASC (LL ASC)-enriched transcriptional program. Whilesome of the differences between LL ASCs and other ASCs appeared to be acquired withage, other features were shared with some younger ASCs, such as high CD138 and CD93.Turnover was unaffected by altered ASC production, arguing against competition forniches as a major driver of turnover. Thus, ASC turnover is set by intrinsic lifespanlimits, with steady-state population dynamics governed by niche vacancy rather thandisplacement.

DOI: 10.1016/j.immuni.2023.04.015

Source: https://www.cell.com/immunity/fulltext/S1074-7613(23)00183-8

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