美国匹兹堡大学Mark J. Shlomchik小组在研究中取得进展。他们的研究认为IL-12诱导B细胞内在的IL-12/IFNγ正反馈循环，促进滤泡外B细胞反应。2024年6月11日出版的《自然—免疫学》发表了这项成果。

该课题组人员发现IL-12是一种细胞因子开关，直接作用于B细胞以促进滤泡外反应并抑制生发中心反应。IL-12在B细胞内启动一个IL-12和IFNγ之间的正反馈循环，放大IFNγ的产生，这与IL-12协同作用，促进小鼠和人类B细胞的增殖和浆母细胞分化。IL-12维持部分IFNγ诱导基因的表达。两者共同引起独特的基因变化，反映了IFNγ的放大作用和两种细胞因子之间的协同效应。

在体内，缺乏IL-12和IFNγ受体的细胞在浆母细胞的产生方面，比仅缺乏其中一个受体的细胞受损更严重。此外，B细胞来源的IL-12增强了浆母细胞反应和T辅助1细胞的分化。因此，B细胞来源的IL-12通过作用于T细胞和B细胞，决定了免疫反应的模式，对疫苗、病原体保护和自身免疫具有重要意义。

据介绍，尽管有些感染会引发生发中心的形成，另一些则仅产生滤泡外反应，但控制这些不同命运的机制尚不完全清楚。

附：英文原文

Title: IL-12 induces a B cell-intrinsic IL-12/IFNγ feed-forward loop promoting extrafollicular B cell responses

Author: Elsner, Rebecca A., Smita, Shuchi, Shlomchik, Mark J.

Issue&Volume: 2024-06-11

Abstract: While some infections elicit germinal centers, others produce only extrafollicular responses. The mechanisms controlling these dichotomous fates are poorly understood. We identify IL-12 as a cytokine switch, acting directly on B cells to promote extrafollicular and suppress germinal center responses. IL-12 initiates a B cell-intrinsic feed-forward loop between IL-12 and IFNγ, amplifying IFNγ production, which promotes proliferation and plasmablast differentiation from mouse and human B cells, in synergy with IL-12. IL-12 sustains the expression of a portion of IFNγ-inducible genes. Together, they also induce unique gene changes, reflecting both IFNγ amplification and cooperative effects between both cytokines. In vivo, cells lacking both IL-12 and IFNγ receptors are more impaired in plasmablast production than those lacking either receptor alone. Further, B cell-derived IL-12 enhances both plasmablast responses and T helper 1 cell commitment. Thus, B cell-derived IL-12, acting on T and B cells, determines the immune response mode, with implications for vaccines, pathogen protection and autoimmunity.

DOI: 10.1038/s41590-024-01858-1

Source: https://www.nature.com/articles/s41590-024-01858-1