美国斯隆凯特林研究所Jayanta Chaudhuri课题组发现，不同的代谢要求调节B细胞的激活和生发中心反应。该研究于2023年6月26日在线发表于国际一流学术期刊《自然—免疫学》杂志上。

研究人员以阶段性和细胞特异性的方式删除乳酸脱氢酶A（LDHA）。结果表明，在一类初始的B细胞中，LDHA的去除并没有深刻地影响其进行细菌脂多糖诱导的细胞外B细胞反应的能力。另一方面，LDHA缺失的初始B细胞在形成生发中心（GC）和发生GC依赖性抗体反应的能力方面有严重缺陷。此外，T细胞中LDHA的缺失严重损害了B细胞依赖的免疫反应。引人注目的是，当LDHA在活化的B细胞而非初始B细胞中被删除时，对GC反应和高亲和力抗体的产生只有很小的影响。这些发现强烈地表明，初始B细胞和活化B细胞有不同的代谢要求，并受到微环境和细胞相互作用的进一步调节。

据悉，感染或疫苗接种后，滤泡外部位或GC内的活化B细胞会发生剧烈的克隆增殖。增殖的淋巴细胞已被证明进行LDHA依赖的有氧糖酵解；然而，这种代谢途径在B细胞从初始状态过渡到高度增殖的活化状态中的具体作用仍未得到明确。

附：英文原文

Title: Distinct metabolic requirements regulate B cell activation and germinal center responses

Author: Sharma, Rahul, Smolkin, Ryan M., Chowdhury, Priyanka, Fernandez, Keith Conrad, Kim, Youngjun, Cols, Montserrat, Alread, William, Yen, Wei-Feng, Hu, Wei, Wang, Zhong-Min, Violante, Sara, Chalign, Ronan, Li, Ming O., Cross, Justin R., Chaudhuri, Jayanta

Issue&Volume: 2023-06-26

Abstract: Following infection or vaccination, activated B cells at extrafollicular sites or within germinal centers (GCs) undergo vigorous clonal proliferation. Proliferating lymphocytes have been shown to undertake lactate dehydrogenase A (LDHA)-dependent aerobic glycolysis; however, the specific role of this metabolic pathway in a B cell transitioning from a nave to a highly proliferative, activated state remains poorly defined. Here, we deleted LDHA in a stage-specific and cell-specific manner. We find that ablation of LDHA in a nave B cell did not profoundly affect its ability to undergo a bacterial lipopolysaccharide-induced extrafollicular B cell response. On the other hand, LDHA-deleted nave B cells had a severe defect in their capacities to form GCs and mount GC-dependent antibody responses. In addition, loss of LDHA in T cells severely compromised B cell-dependent immune responses. Strikingly, when LDHA was deleted in activated, as opposed to nave, B cells, there were only minimal effects on the GC reaction and in the generation of high-affinity antibodies. These findings strongly suggest that nave and activated B cells have distinct metabolic requirements that are further regulated by niche and cellular interactions.

DOI: 10.1038/s41590-023-01540-y

Source: https://www.nature.com/articles/s41590-023-01540-y