血吞噬淋巴组织细胞增多症（HLH）以高炎症和多器官功能障碍为特征。感染，包括病毒复活，对HLH的疾病致死率有重要贡献。虽然T和NK细胞驱动的免疫活化和失调已有详细描述，但关于HLH中B细胞组分和体液免疫功能的数据有限。我们注意到患有活动性HLH的患者中早期B细胞发育受到显著抑制。在体外使用HLH定义的细胞因子，如干扰素-γ（IFN-g）和肿瘤坏死因子，进行B细胞分化研究，复制了B细胞发育阻滞。使用IFN-g暴露的人类CD34+细胞的mRNA测序显示了影响B细胞发育和成熟的基因和通路的变化。此外，患有活动性HLH的患者表现出类转换记忆B（CSMB）细胞的明显减少和骨髓浆细胞/浆细胞区的减少。CSMB细胞的减少与循环滤泡辅助T细胞（cTfh）细胞的减少相关。最后，在一个HLH患者的淋巴结和脾脏评估中发现缺乏克隆中心形成和与淋巴细胞减少相关的巨噬细胞吞噬。令人放心的是，控制T细胞活化后CSMB和cTfh的频率得到改善。综上所述，在活动性HLH患者中，这些B细胞的变化可能影响体液免疫反应；然而，需要进一步的免疫研究来确定其临床意义。版权所有©2023美国血液学会。

Hemophagocytic lymphohistiocytosis (HLH) is characterized by hyperinflammation and multi-organ dysfunction. Infections, including the reactivation of viruses, contribute to significant disease mortality in HLH. While T and NK cell-driven immune activation and dysregulation are well described, limited data exist on the status of the B cell compartment and humoral immune function in HLH. We noted marked suppression of early B cell development in patients with active HLH. In vitro B cell differentiation studies following exposure to HLH-defining cytokines, such as interferon-gamma (IFN-g) and tumor necrosis factor, recapitulated B cell development arrest. mRNA sequencing of human CD34+ cells exposed to IFN-g demonstrated changes in genes and pathways affecting B cell development and maturation. In addition, patients with active HLH exhibited a marked decrease in class-switched memory B (CSMB) cells and a decrease in bone marrow plasmablast/plasma cell compartments. The decrease in CSMB cells was associated with a decrease in circulating T follicular helper (cTfh) cells. Finally, lymph node and spleen evaluation in a patient with HLH revealed absent germinal center formation and hemophagocytosis with associated lymphopenia. Reassuringly, the frequency of CSMB and cTfh improved with control of T cell activation. Taken together, in patients with active HLH, these changes in B cells may affect the humoral immune response; however, further immune studies are needed to determine its clinical significance.Copyright © 2023 American Society of Hematology.