Dataset Information

Selection of apoptotic cell specific human antibodies from adult bone marrow.

ABSTRACT: Autoreactive antibodies that recognize neo-determinants on apoptotic cells in mice have been proposed to have protective, homeostatic and immunoregulatory properties, although our knowledge about the equivalent antibodies in humans has been much more limited. In the current study, human monoclonal antibodies with binding specificity for apoptotic cells were isolated from the bone marrow of healthy adults using phage display technology. These antibodies were shown to recognize phosphorylcholine (PC)-associated neo-determinants. Interestingly, three of the four identified apoptotic cell-specific antibody clones were encoded by VH3 region rearrangements with germline or nearly germline configuration without evidence of somatic hypermutation. Importantly, the different identified antibody clones had diverse heavy chain CDR3 and deduced binding surfaces as suggested by structure modeling. This may suggest a potentially great heterogeneity in human antibodies recognizing PC-related epitopes on apoptotic cells. To re-construct the postulated structural format of the parental anti-PC antibody, the dominant clone was also expressed as a recombinant human polymeric IgM, which revealed a substantially increased binding reactivity, with dose-dependent and antigen-inhibitable binding of apoptotic cells. Our findings may have implication for improved prognostic testing and therapeutic interventions in human inflammatory disease.

SUBMITTER: Gronwall C

PROVIDER: S-EPMC3997490 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Selection of apoptotic cell specific human antibodies from adult bone marrow.

Grönwall Caroline C Charles Edgar D ED Dustin Lynn B LB Rader Christoph C Silverman Gregg J GJ

PloS one 20140423 4

Autoreactive antibodies that recognize neo-determinants on apoptotic cells in mice have been proposed to have protective, homeostatic and immunoregulatory properties, although our knowledge about the equivalent antibodies in humans has been much more limited. In the current study, human monoclonal antibodies with binding specificity for apoptotic cells were isolated from the bone marrow of healthy adults using phage display technology. These antibodies were shown to recognize phosphorylcholine ( ...[more]

PMID: 24760047

Similar Datasets

Project description:Childhood immunization with the live-attenuated varicella-zoster virus (VZV) vaccine induces protective immune responses. Routine VZV vaccination started only 2 decades ago, and thus, there are few studies examining the longevity of vaccine-induced immunity. Here, we analyzed the quantity of VZV-specific plasma cells (PCs) and CD4 T cells in the bone marrow (BM) of healthy young adults (n = 15) following childhood VZV immunization. Long-lived BM resident plasma cells constitutively secrete antibodies, and we detected VZV-specific PCs in the BM of all subjects. Anti-VZV plasma antibody titers correlated positively with the number of VZV-specific BM PCs. Furthermore, we quantified the number of interferon gamma (IFN-γ)-producing CD4 T cells specific for VZV glycoprotein E and all other structural and nonstructural VZV proteins in both BM and blood (peripheral blood mononuclear cells [PBMCs]). The frequency of VZV-specific IFN-γ-producing CD4 T cells was significantly higher in PBMCs than BM. Our study shows that VZV-specific PCs and VZV-specific CD4 memory T cells persist up to 20 years after vaccination. These findings indicate that childhood VZV vaccination can elicit long-lived immune memory responses in the bone marrow.IMPORTANCE Childhood varicella-zoster virus (VZV) immunization induces immune memory responses that protect against primary VZV infection, chicken pox. In the United States, routine childhood VZV vaccination was introduced only 2 decades ago. Hence, there is limited information on the longevity of B and CD4 T cell memory, which are both important for protection. Here, we showed in 15 healthy young adults that VZV-specific B and CD4 T cell responses are detectable in bone marrow (BM) and blood up to 20 years after vaccination. Specifically, we measured antibody-secreting plasma cells in the BM and VZV-specific CD4 T cells in BM and blood. These findings suggest that childhood VZV vaccination induces long-lived immunity.

Project description:BACKGROUND: Cell-derived microvesicles (MVs) have been described as a new mechanism of cell-to-cell communication. MVs after internalization within target cells may deliver genetic information. Human bone marrow derived mesenchymal stem cells (MSCs) and liver resident stem cells (HLSCs) were shown to release MVs shuttling functional mRNAs. The aim of the present study was to evaluate whether MVs derived from MSCs and HLSCs contained selected micro-RNAs (miRNAs). METHODOLOGY/PRINCIPAL FINDINGS: MVs were isolated from MSCs and HLSCs. The presence in MVs of selected ribonucleoproteins involved in the traffic and stabilization of RNA was evaluated. We observed that MVs contained TIA, TIAR and HuR multifunctional proteins expressed in nuclei and stress granules, Stau1 and 2 implicated in the transport and stability of mRNA and Ago2 involved in miRNA transport and processing. RNA extracted from MVs and cells of origin was profiled for 365 known human mature miRNAs by real time PCR. Hierarchical clustering and similarity analysis of miRNAs showed 41 co-expressed miRNAs in MVs and cells. Some miRNAs were accumulated within MVs and absent in the cells after MV release; others were retained within the cells and not secreted in MVs. Gene ontology analysis of predicted and validated targets showed that the high expressed miRNAs in cells and MVs could be involved in multi-organ development, cell survival and differentiation. Few selected miRNAs shuttled by MVs were also associated with the immune system regulation. The highly expressed miRNAs in MVs were transferred to target cells after MV incorporation. CONCLUSIONS: This study demonstrated that MVs contained ribonucleoproteins involved in the intracellular traffic of RNA and selected pattern of miRNAs, suggesting a dynamic regulation of RNA compartmentalization in MVs. The observation that MV-highly expressed miRNAs were transferred to target cells, rises the possibility that the biological effect of stem cells may, at least in part, depend on MV-shuttled miRNAs. Data generated from this study, stimulate further functional investigations on the predicted target genes and pathways involved in the biological effect of human adult stem cells.

Dataset Information

Selection of apoptotic cell specific human antibodies from adult bone marrow.

Publications

Selection of apoptotic cell specific human antibodies from adult bone marrow.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets