Humoral Immune Reconstitution Kinetics after Allogeneic Hematopoietic Stem Cell Transplantation in Children: A Maturation Block of IgM Memory B Cells.

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Presentation transcript:

Humoral Immune Reconstitution Kinetics after Allogeneic Hematopoietic Stem Cell Transplantation in Children: A Maturation Block of IgM Memory B Cells May Lead to Impaired Antibody Immune Reconstitution Hisham Abdel-Azim, Amro Elshoury, Kris M. Mahadeo, Robertson Parkman, Neena Kapoor Biology of Blood and Marrow Transplantation Volume 23, Issue 9, Pages 1437-1446 (September 2017) DOI: 10.1016/j.bbmt.2017.05.005 Copyright © 2017 The American Society for Blood and Marrow Transplantation Terms and Conditions

Figure 1 B lymphocyte maturation. Transitional B lymphocytes are the first B lymphocytes to leave the bone marrow, and when they reach the spleen, they can develop into either naive or IgM-memory B lymphocyte. Transitional B lymphocytes express toll-like receptor-9, which upon exposure to unmethylated bacterial DNA (CpG) can generates IgM memory B lymphocytes. Naive B lymphocytes leave the spleen and after antigen exposure in the germinal center can develop into switched memory and plasma B lymphocytes. Switched memory B lymphocytes, require T lymphocyte costimulation to produce high-affinity antibodies, including IgG and IgA, within the germinal centers of lymphoid tissues. On the other hand, IgM memory B lymphocytes are similar to marginal zone B cells in the spleen and respond to infections or vaccination by producing low-affinity IgM antibody. Biology of Blood and Marrow Transplantation 2017 23, 1437-1446DOI: (10.1016/j.bbmt.2017.05.005) Copyright © 2017 The American Society for Blood and Marrow Transplantation Terms and Conditions

Figure 2 Specific antibody responses (anti-PRP and TT antibodies) after allo-HSCT. Medians for TT antibodies (A) anti-PRP (B) are represented for each time point after HSCT. Normal values (healthy immune controls [21]) are represented by a black line in each panel. The number of patients in each time point after HSCT is listed below each bar. Biology of Blood and Marrow Transplantation 2017 23, 1437-1446DOI: (10.1016/j.bbmt.2017.05.005) Copyright © 2017 The American Society for Blood and Marrow Transplantation Terms and Conditions

Figure 3 Naive, IgM, and switched memory B cells immune reconstitution after allo-HSCT. Medians for naive (A), IgM (B), and switched (C) memory B cells are represented for each time point after HSCT, compared with normal values (healthy controls). Statistically significant P values (P < .05) are represented as an asterisk (*) symbol. The number of patients in each time point after HSCT is listed below each bar. Biology of Blood and Marrow Transplantation 2017 23, 1437-1446DOI: (10.1016/j.bbmt.2017.05.005) Copyright © 2017 The American Society for Blood and Marrow Transplantation Terms and Conditions

Figure 4 Correlation between memory B cell and specific antibodies (anti-PRP and TT antibodies) at 1 year after allo-HSCT (n = 69). (A) Correlation between IgM memory B cells and both anti-PRP and TT antibodies. (B) Correlation between switched memory B cells and both anti-PRP and TT antibodies. Statistically significant P values (P < .05) are represented as an asterisk (*) symbol. Biology of Blood and Marrow Transplantation 2017 23, 1437-1446DOI: (10.1016/j.bbmt.2017.05.005) Copyright © 2017 The American Society for Blood and Marrow Transplantation Terms and Conditions

Figure 5 Correlation (n = 71) between CD4 T cells and switched memory B cells at 6 months after HSCT. Statistically significant P values (P < .05) are represented as an asterisk (*) symbol. Biology of Blood and Marrow Transplantation 2017 23, 1437-1446DOI: (10.1016/j.bbmt.2017.05.005) Copyright © 2017 The American Society for Blood and Marrow Transplantation Terms and Conditions

Figure 6 Effect of TBI on specific antibody response (anti-PRP and TT antibodies), naive and memory B cell immune reconstitution. Medians for TT-antibody (A), anti-PRP antibody (B), naive (C), IgM (D), switched (E) memory B cells, and CD4 T cells (F) are represented after HSCT. Normal values (healthy immune controls [21]) are represented by a black line in each panel. Statistically significant P values (P < .05) are represented as asterisk (*) symbol. The number of patients in each time point after HSCT is listed below each bar. Biology of Blood and Marrow Transplantation 2017 23, 1437-1446DOI: (10.1016/j.bbmt.2017.05.005) Copyright © 2017 The American Society for Blood and Marrow Transplantation Terms and Conditions

Figure 7 Effect of cGVHD on naive, IgM. and switched memory B cells immune reconstitution. Medians for naive (A), IgM (B) and switched (C) memory B cells are represented for each time point after HSCT and compared with recipients with extensive cGVHD. Normal values (healthy controls) are represented by a black line in each panel. Statistically significant P values (P < .05) are represented as asterisk (*) symbol. The number of patients in each time point after HSCT is listed below each bar. Biology of Blood and Marrow Transplantation 2017 23, 1437-1446DOI: (10.1016/j.bbmt.2017.05.005) Copyright © 2017 The American Society for Blood and Marrow Transplantation Terms and Conditions

Figure 8 Effect of the source of stem cells on naive, IgM and memory B cell immune reconstitution. Medians for naive (A), IgM (B) and switched (C) memory B cells at 6 months after HSCT (n = 18, 39, and 14 for CB, BM and PBSC, respectively) . Normal values (healthy controls) are represented by a black line in each panel. Statistically significant P values (P < .05) are represented as an asterisk (*) symbol. Biology of Blood and Marrow Transplantation 2017 23, 1437-1446DOI: (10.1016/j.bbmt.2017.05.005) Copyright © 2017 The American Society for Blood and Marrow Transplantation Terms and Conditions