title: Distinctions among Circulating Antibody-Secreting Cell Populations, Including B-1 Cells, in Human Adult Peripheral Blood.
abstract: Human Ab-secreting cell (ASC) populations in circulation are not well studied. In addition to B-1 (CD20(+)CD27(+)CD38(lo/int)CD43(+)) cell and conventional plasmablast (PB) (CD20-CD27(hi)CD38(hi)) cell populations, in this study, we identified a novel B cell population termed 20(+)38(hi) B cells (CD20(+)CD27(hi)CD38(hi)) that spontaneously secretes Ab. At steady-state, 20(+)38(hi) B cells are distinct from PBs on the basis of CD20 expression, amount of Ab production, frequency of mutation, and diversity of BCR repertoire. However, cytokine treatment of 20(+)38(hi) B cells induces loss of CD20 and acquisition of CD138, suggesting that 20(+)38(hi) B cells are precursors to PBs or pre-PBs. We then evaluated similarities and differences among CD20(+)CD27(+)CD38(lo/int)CD43(+) B-1 cells, CD20(+)CD27(hi)CD38(hi) 20(+)38(hi) B cells, CD20(-)CD27(hi)CD38(hi) PBs, and CD20(+)CD27(+)CD38(lo/int)CD43(-) memory B cells. We found that B-1 cells differ from 20(+)38(hi) B cells and PBs in a number of ways, including Ag expression, morphological appearance, transcriptional profiling, Ab skewing, Ab repertoire, and secretory response to stimulation. In terms of gene expression, B-1 cells align more closely with memory B cells than with 20(+)38(hi) B cells or PBs, but differ in that memory B cells do not express Ab secretion-related genes. We found that B-1 cell Abs use Vh4-34, which is often associated with autoreactivity, 3- to 6-fold more often than other B cell populations. Along with selective production of IgM anti-phosphoryl choline, these data suggest that human B-1 cells might be preferentially selected for autoreactivity/natural specificity. In summary, our results indicate that human healthy adult peripheral blood at steady-state consists of three distinct ASC populations.
authors.affiliation: Center for Oncology and Cell Biology, The Feinstein Institute for Medical Research, Manhasset, NY 11030;
authors.forename: Tâm D
authors.initials: TD
authors.lastname: Quách
authors.affiliation: Center for Oncology and Cell Biology, The Feinstein Institute for Medical Research, Manhasset, NY 11030; Tumor Immunology Direction, Center for Molecular Immunology, Havana 11600, Cuba; and.
authors.forename: Nely
authors.identifier: http://orcid.org/0000-0002-2070-3016
authors.initials: N
authors.lastname: Rodríguez-Zhurbenko
authors.affiliation: Center for Oncology and Cell Biology, The Feinstein Institute for Medical Research, Manhasset, NY 11030;
authors.forename: Thomas J
authors.identifier: http://orcid.org/0000-0002-0670-4872
authors.initials: TJ
authors.lastname: Hopkins
authors.affiliation: Center for Oncology and Cell Biology, The Feinstein Institute for Medical Research, Manhasset, NY 11030;
authors.forename: Xiaoti
authors.initials: X
authors.lastname: Guo
authors.affiliation: Center for Oncology and Cell Biology, The Feinstein Institute for Medical Research, Manhasset, NY 11030; Tumor Immunology Direction, Center for Molecular Immunology, Havana 11600, Cuba; and.
authors.forename: Ana María
authors.identifier: http://orcid.org/0000-0003-2111-1677
authors.initials: AM
authors.lastname: Hernández
authors.affiliation: Robert S. Boas Center for Genomics and Human Genetics, The Feinstein Institute for Medical Research, Manhasset, NY 11030.
authors.forename: Wentian
authors.identifier: http://orcid.org/0000-0003-1155-110X
authors.initials: W
authors.lastname: Li
authors.affiliation: Center for Oncology and Cell Biology, The Feinstein Institute for Medical Research, Manhasset, NY 11030; tr@nshs.edu.
authors.forename: Thomas L
authors.initials: TL
authors.lastname: Rothstein
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000032:analysis / Q000096:biosynthesis / Q000276:immunology; D016175:B-Lymphocyte Subsets / Q000166:cytology* / Q000276:immunology*; D002469:Cell Separation; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007156:Immunologic Memory / Q000276:immunology; D016130:Immunophenotyping; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055815:Young Adult
chemical_list: D015703:Antigens, CD