Lasaviciute Gintare, Bricaud Andréas L, Hellgren Fredrika, Ingelman-Sundberg Hanna M, Eksborg Staffan, Jonker Margreet, Haanstra Krista G, Hed Myrberg Ida, Sverremark-Ekström Eva, Loré Karin, Saghafian-Hedengren Shanie, Nilsson Anna
Departmet of Molecular Biosciences The Wenner-Gren Institute Stockholm University Stockholm Sweden.
Childhood Cancer Research Unit Department of Women's and Children's Health Karolinska Institutet Stockholm Sweden.
Clin Transl Immunology. 2020 Jul 2;9(7):e1150. doi: 10.1002/cti2.1150. eCollection 2020.
Loss of vaccine-induced antibodies (Abs) after chemotherapy against paediatric acute lymphoblastic leukaemia (ALL) is common and often necessitates re-immunisation after cessation of treatment. Even so, some ALL survivors fail to mount or to maintain protective Abs. Germinal centres (GCs) are clusters of proliferating B cells in follicles of secondary lymphoid tissues (SLTs) formed during adaptive immune responses and the origins of long-lived memory B and plasma cells that are the source of Abs. Furthermore, productive GC reactions depend on T follicular helper (T) cells. To understand why chemotherapy induces deficits in Ab responses, we examined how SLTs were affected by chemotherapy.
Rhesus macaques were infused with either three cycles of the anthracycline doxorubicin or saline, followed by immunisation with a and booster antigen. Spleen and lymph nodes were removed, and memory B, bulk T and T cells were examined.
Despite adequate GC morphology, a diminished memory and IgG B-cell population along with diminished total and booster vaccine-specific IgG-producing memory B cells were noted in the spleens of macaques with past doxorubicin exposure compared to the saline-treated controls ( < 0.05). Intact bulk T and T cells were found in the SLTs of treated macaques, which displayed higher CD40L upregulation capacity by their splenic CXCR5 helper T cells ( < 0.01). In contrast to the spleen, the immune cell populations studied were comparable between the lymph nodes of both saline- and doxorubicin-treated macaques.
Our findings suggest that the splenic memory B-cell subset, compared to its lymph node counterpart, is more severely altered by anthracycline treatment.
小儿急性淋巴细胞白血病（ALL）化疗后疫苗诱导抗体（Abs）丧失很常见，治疗结束后通常需要重新免疫。即便如此，一些ALL幸存者仍无法产生或维持保护性抗体。生发中心（GCs）是在适应性免疫反应期间形成的次级淋巴组织（SLTs）滤泡中增殖B细胞的簇集，是长寿记忆B细胞和浆细胞的来源，而这些细胞是抗体的来源。此外，有效的GC反应依赖于滤泡辅助性T（TFH）细胞。为了解化疗为何会导致抗体反应缺陷，我们研究了化疗对SLTs的影响。
给恒河猴输注三个周期的蒽环类药物阿霉素或生理盐水，随后用抗原和加强抗原进行免疫。切除脾脏和淋巴结，检查记忆B细胞、总T细胞和TFH细胞。
与生理盐水处理的对照组相比，既往暴露于阿霉素的猕猴脾脏中，尽管GC形态正常，但记忆B细胞和IgG B细胞群体减少，总疫苗特异性IgG产生记忆B细胞和加强疫苗特异性IgG产生记忆B细胞也减少（P<0.05）。在接受治疗的猕猴的SLTs中发现完整的总T细胞和TFH细胞，其脾脏CXCR5辅助性T细胞显示出更高的CD40L上调能力（P<0.01）。与脾脏不同，生理盐水处理和阿霉素处理的猕猴淋巴结之间，所研究的免疫细胞群体相当。
我们的研究结果表明，与淋巴结中的记忆B细胞亚群相比，蒽环类药物治疗对脾脏记忆B细胞亚群的改变更为严重。
