Reconstitution of the B cell repertoire after bone marrow transplantation does not recapitulate human fetal development

Abstract

Summary:Immune reconstitution during bone marrow transplantation has been proposed to produce a fetal-type immune system. This characteristic may contribute to the relative immunodeficiency that occurs in the early post-transplant period. This review reappraises recent studies of immunoglobulin heavy chain genes produced by the recovering immune system. Comparison of these genes to those that are generated by fetal and adult B cells, demonstrates that there is no evidence to support the conclusion that adult lymphocytes in the graft reverse to a fetal stage of differentiation. In terms of lymphocyte diversity, the inadequacy of the recovering immune system is more likely to be explained by a combination of other factors -such as the delayed occurrence of somatic hypermutation and class switching, and clonal dominance. Keywords: immune reconstitution; immunoglobulin; repertoire development; CDR3; diversity; fetus The purpose of stemcell/bone marrow transplantation (BMT) is transfer of a functional immune system to an immunocompromised recipient. The early period after BMT, however, is characterized by cellular and humoral immunodeficiency which can last for months to years. Whereas components of non-specific immunity (granulocytes, monocytes/macrophages and NK cells) recover within 2-6 months, functional recovery of B and T lymphocytes can take up to 2 years or longer. 1 Many factors contributing to this slow recovery have been identified, such as the immunosuppressive effect of high-dose radio/chemotherapy, the effect of graft-versus-host disease (GVHD), treatment of GVHD by immunosuppressants and decreased thymic function in older patients.Serological studies and analysis of cell surface marker expression showed that reconstitution of humoral immunocompetence follows patterns previously described in neonates. [2][3][4][5][6] Antibodies against protein and conjugated polysaccharide antigens predate immune responses against carboCorrespondence: Dr FM Raaphorst,

Allogeneic stem cell transplantation: low immunoglobulin levels associated with decreased survival

“…1,2 Parts of the innate immune system, such as granulocytes, monocytes and NK cells, recover within 2-6 months after SCT. 3 Patients who develop chronic GVHD after SCT may never recover normal immune function.…”

Crucial role of FLT3 ligand in immune reconstitution after bone marrow transplantation and high-dose chemotherapy

“…2 Low levels of B cells and immunoglobulins, as well as reduced CD4 T cells, predispose transplant recipients to severe bacterial (such as Streptococcus pneumoniae or Haemophilus influenzae) and opportunistic viral infections (such as cytomegalovirus, EpsteinBarr virus, and herpes). 1,[3][4][5][6] Consequently, significant efforts have been pursued to develop more efficient means of accelerating immune recovery after BMT. Whereas the identification of granulocyte colony-stimulating factor and granulocyte/monocyte colony-stimulating factor has been used to successfully promote clinical granulocyte recovery, 7 no cytokine treatment has been developed to accelerate B-and T-cell reconstitution after myeloablation and BMT.…”

Flow cytometric immunophenotyping in the diagnosis and follow-up of immunodeficient children

“…The slow reconstitution of lymphocytes after bone marrow transplantation [2] can be monitored by a simple immunophenotyping protocol to determine the numbers of the main lymphocyte populations (``limited'' protocol in Table 2). It should be kept in mind, however, that functional restoration of the lymphoid system takes more time than is needed for the normalisation of absolute counts [22]. HIV infection is generally diagnosed by serology or polymerase chain reaction.…”