The Contribution of Large Granular Lymphocytes to B Cell Activation and Differentiation After T-Cell-Depleted Allogeneic Bone Marrow Transplantation

Brenner, Malcolm K.; Reittie, J. E.; Grob, J. P.; Wimperis, J. Z.; Stephens, Susan; Patterson, J.; Hoffbrand, A. V.; Prentice, HG

doi:10.1097/00007890-198609000-00006

Cited by 37 publications

(13 citation statements)

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“…37,38 In infant recipients who were partially immunized, the sustained production of antibody to specific vaccine antigen may be related not only to the helper effects by the thymus-dependent regeneration of CD4 ϩ T lymphocytes, but also by the relatively large numbers of NK cells found in these infants (Figure 3a). 39,40 This study has several limitations. First, the size of the cohort and the duration of follow-up are limited.…”

Section: Discussionmentioning

confidence: 96%

Allogeneic bone marrow transplantation for infants with acute leukemia or myelodysplastic syndrome

Leung

Pitts

Burnette

et al. 2001

Bone Marrow Transplant

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Summary:The objective of this study is to investigate the outcome of children 24 months of age or younger (infants) at the time of allogeneic bone marrow transplantation (BMT) for acute leukemia or myelodysplasia. We analyzed the survival rate, prognostic factors, incidences of late sequelae, and immune reconstitution in 22 infants who underwent allogeneic BMT. The 5-year event-free survival estimate was 45.5% (95% confidence interval (CI), 24.4% to 63.3%). Six patients died of transplant-related complications and six died of disease relapse. Remission status at the time of BMT was the most important prognostic factor (P ‫؍‬ 0.005): no patient who received a transplant while their disease was not in remission survived, whereas the 5-year survival estimate for infants who underwent BMT during remission was 56% (95% CI, 31% to 75%). Long-term outcomes in the 10 infant survivors were compared with those of 10 older controls matched for diagnosis, disease status at the time of BMT, calendar year at the time of BMT, and source of stem cells. Immune function 1 year after transplantation and the incidences and spectra of late sequelae were similar for both groups during a median of 3.5 years (range, 1.5 to 7.2 years) of follow-up. Bone Marrow Transplantation (2001) 27, 717-722. Keywords: allogeneic transplantation; infant leukemia; myelodysplastic syndrome; late sequelaeThe incidences of lymphoid and myeloid leukemias in infants are approximately equal. Acute lymphoblastic leukemia (ALL) in infants accounts for 2.5% to 5% of all cases of childhood ALL, and acute myeloid leukemia (AML) in infants accounts for 6% to 14% of all cases of childhood AML. 1 The frequent presence of poor prognostic factors such as 11q23/MLL rearrangement in ALL and a high leukocyte count at the time of diagnosis of AML results in an overall long-term survival of only approxiCorrespondence: WH Leung,

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Section: Discussionmentioning

confidence: 96%

Allogeneic bone marrow transplantation for infants with acute leukemia or myelodysplastic syndrome

Leung

Pitts

Burnette

et al. 2001

Bone Marrow Transplant

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“…In recipients of T cell-depleted allogeneic bone marrow transplants, large granular lymphocytes which contain mostly NK cells were found responsible for the secretion of B cell differentiation factors capable of maintaining the Ig expression and specific Ab levels in the absence of mature T cells. It appears likely that NK cells play a significant role in maintaining B cell function in vivo upon T cell-depleted BMT (10,45). Donor type-activated NK cells have also been shown to promote BMT in mice (9).…”

Section: Discussionmentioning

confidence: 99%

“…For example, it has been shown that NK cells are involved in the regulation of B lymphocyte functions (5)(6)(7)(8). Donor type-activated NK cells promote marrow engraftment and B cell development during allogeneic bone marrow transplantation in mice (9) and in humans (10). Also, human NK cells can enhance the B cell proliferative responses to the surface Ig cross-linking agents anti-IgM or Staphylococcus aureus Cowan strain (6).…”

Section: Cd2mentioning

confidence: 99%

Human B Cell Activation by Autologous NK Cells Is Regulated by CD40-CD40 Ligand Interaction: Role of Memory B Cells and CD5+ B Cells

Blanca

Bere

Young

et al. 2001

The Journal of Immunology

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NK cells are a subpopulation of lymphocytes characterized primarily by their cytolytic activity. They are recognized as an important component of the immune response against virus infection and tumors. In addition to their cytolytic activity, NK cells also participate either directly or indirectly in the regulation of the ongoing Ab response. More recently, it has been suggested that NK cells have an important role in the outcome of autoimmune diseases. Here, we demonstrate that human NK cells can induce autologous resting B cells to synthesize Ig, including switching to IgG and IgA, reminiscent of a secondary Ab response. B cell activation by the NK cell is contact-dependent and rapid, suggesting an autocrine B cell-regulated process. This NK cell function is T cell-independent, requires an active cytoplasmic membrane, and is blocked by anti-CD40 ligand (anti-CD154) or CD40-mIg fusion protein, indicating a critical role for CD40-CD40 ligand interaction. Depletion studies also demonstrate that CD5+ B cells (autoreactive B-1 cells) and a heterogeneous population of CD27+ memory B cells play a critical role in the Ig response induced by NK cells. The existence of this novel mechanism of B cell activation has important implications in innate immunity, B cell-mediated autoimmunity, and B cell neoplasia.

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“…T LGL proliferation follows a chronic course during which major features are neutropenia, anemia, bone marrow infiltration, mild splenomegaly and multiple immune abnormalities (polyclonal hypergammaglobulinemia presence of rheumatoid factor, autoimmune antibodies and circulating immune complexes). 4,5 Persistently elevated numbers of CD8 + CD57 + lymphocytes have been shown to be increased in a few cases after allogeneic stem cell transplantation (allo-SCT) with myeloablative conditioning regimens, [6][7][8][9] or following solid organ transplantation. 10 However, the clinical features of this entity in the allo-SCT setting are still sparse.…”

Section: Introductionmentioning

confidence: 99%

Features of large granular lymphocytes (LGL) expansion following allogeneic stem cell transplantation: a long-term analysis

et al. 2002

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Large granular lymphocyte (LGL) proliferation typically follows a chronic course during which major features are cytopenia and immune abnormalities. Elevated numbers of LGL were reported in a few cases following allogeneic stem cell transplantation (allo-SCT). In this report, we present a retrospective analysis of LGL cases that occurred following allo-SCT in a cohort of 201 consecutive patients transplanted over a period of 7 years. Six cases were identified and LGL expansion occurred more frequently following a reduced fludarabine and anti-T lymphocyte globulin-based preparative regimen (4 cases/49), than after a conventional myeloablative regimen (2 cases/152). Expansion of LGL was seen between 3 and 15 months following allo-SCT. Hematopoiesis, with mild to severe cytopenia, was a favored target for LGL. Autoimmune manifestations including polyarthritis and hypergammaglobulinemia were also observed. LGL proliferation was observed in the context of chronic antigenic stimulation associated with recurrent viral infections especially CMV. Moreover, five out of these six high risk patients achieved a long-term complete remission concomitant or following LGL expansion. These data suggest that LGL might be a subset of effector lymphocytes which may participate to the graft-versus-tumor effect.

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The Contribution of Large Granular Lymphocytes to B Cell Activation and Differentiation After T-Cell-Depleted Allogeneic Bone Marrow Transplantation

Cited by 37 publications

References 0 publications

Allogeneic bone marrow transplantation for infants with acute leukemia or myelodysplastic syndrome

Allogeneic bone marrow transplantation for infants with acute leukemia or myelodysplastic syndrome

Human B Cell Activation by Autologous NK Cells Is Regulated by CD40-CD40 Ligand Interaction: Role of Memory B Cells and CD5+ B Cells

Features of large granular lymphocytes (LGL) expansion following allogeneic stem cell transplantation: a long-term analysis

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