Deficits in the IgG+ memory B‐cell recovery after anthracycline treatment is confined to the spleen of rhesus macaques

• Published in: Clinical & translational immunology Vol. 9; no. 7; pp. e1150 - n/a
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: Australia John Wiley & Sons, Inc 2020; John Wiley and Sons Inc; Wiley
• Subjects: Acute lymphoblastic leukemia; Adaptive immunity; Animals; Anthracycline; Antigens; CD40L protein; Chemotherapy; CXCR5 protein; Cytology; de novo and booster vaccine; de novoand booster vaccine; Doxorubicin; Follicles; Germinal centers; Immunization; Immunoglobulin G; Immunological memory; Immunology; Leukemia; Lymph nodes; Lymphocytes; Lymphocytes B; Lymphocytes T; Lymphoid tissue; Measles; Medicin och hälsovetenskap; memory B-cell response; Memory cells; Original; Plasma cells; Population; Population studies; rhesus macaque; secondary lymphoid organs; Spleen; Vaccines; secondary lymphoid organs; rhesus macaque; anthracycline; memory B‐cell response; de novo and booster vaccine
• ISSN: 2050-0068; 2050-0068
• DOI: 10.1002/cti2.1150

Objectives 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 (TFH) cells. To understand why chemotherapy induces deficits in Ab responses, we examined how SLTs were affected by chemotherapy. Methods Rhesus macaques were infused with either three cycles of the anthracycline doxorubicin or saline, followed by immunisation with a de novo and booster antigen. Spleen and lymph nodes were removed, and memory B, bulk T and TFH cells were examined. Results 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 (P < 0.05). Intact bulk T and TFH cells were found in the SLTs of treated macaques, which displayed higher CD40L upregulation capacity by their splenic CXCR5+ helper T cells (P < 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. Conclusion Our findings suggest that the splenic memory B‐cell subset, compared to its lymph node counterpart, is more severely altered by anthracycline treatment. In this study, we found that the recovery of IgG‐producing memory B cells in the spleen lags behind after cessation of anthracycline treatment, a widely used drug in acute lymphoblastic leukaemia protocols. This finding was accompanied by impaired splenic B‐cell response to booster antigen, raising the possibility of residual damage to serological memory after treatment of blood cancers.