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Bone marrow plasma cells are a primary source of serum HIV-1-specific antibodies in chronically infected individuals.
- Source :
-
Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2015 Mar 15; Vol. 194 (6), pp. 2561-8. Date of Electronic Publication: 2015 Feb 13. - Publication Year :
- 2015
-
Abstract
- Several potent and broadly neutralizing Abs to HIV-1 have been isolated recently from peripheral blood B cells of infected individuals, based on prescreening of Ab activity in the serum. However, little is known regarding the cells that make the Abs that circulate in the blood. Accordingly, we investigated the most likely source, the bone marrow, of chronically HIV-1-infected individuals who were not receiving antiretroviral therapy. Increased frequencies of plasma cells, as well as B cell precursors, namely preB-I and preB-II, and decreased frequencies of mature B cells were observed in bone marrow aspirates of these individuals compared with HIV-negative counterparts. Increased frequencies of bone marrow plasma cells are consistent with known hallmarks of HIV-1 infection, namely hypergammaglobulinemia and increased frequencies of peripheral blood plasmablasts. Levels of HIV-1 envelope (Env)-binding and HIV-1-neutralizing Abs were measured in serum, and corresponding frequencies of Ab-secreting or Env-binding cells were measured in the blood (plasmablasts and memory B cells) and in the bone marrow (plasma cells). A strong correlation was observed between serum HIV-1-specific Abs and Env-specific bone marrow-derived plasma cells, but not circulating plasmablasts or memory B cells. These findings demonstrate that, despite HIV-1-induced phenotypic and functional B cell dysregulation in the peripheral blood and secondary lymphoid tissues, bone marrow plasma cells remain a primary source for circulating HIV-1-specific Abs in HIV-1-infected individuals.
- Subjects :
- Adult
Antibodies, Neutralizing blood
Antibodies, Neutralizing immunology
B-Lymphocyte Subsets immunology
B-Lymphocyte Subsets metabolism
B-Lymphocytes immunology
B-Lymphocytes metabolism
Bone Marrow immunology
Bone Marrow virology
Bone Marrow Cells metabolism
Enzyme-Linked Immunosorbent Assay
Female
Flow Cytometry
HIV Antibodies blood
HIV Infections blood
HIV Infections virology
HIV-1 physiology
Host-Pathogen Interactions immunology
Humans
Immunologic Memory immunology
Lymphocyte Count
Male
Plasma Cells metabolism
Precursor Cells, B-Lymphoid immunology
Precursor Cells, B-Lymphoid metabolism
Young Adult
env Gene Products, Human Immunodeficiency Virus immunology
env Gene Products, Human Immunodeficiency Virus metabolism
Bone Marrow Cells immunology
HIV Antibodies immunology
HIV Infections immunology
HIV-1 immunology
Plasma Cells immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1550-6606
- Volume :
- 194
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Journal of immunology (Baltimore, Md. : 1950)
- Publication Type :
- Academic Journal
- Accession number :
- 25681347
- Full Text :
- https://doi.org/10.4049/jimmunol.1402424