Sustained secretion of immunoglobulin by long-lived human tonsil plasma cells.
Immunoglobulin-secreting cells comprise both short-lived proliferating plasmablasts and long-lived nonproliferating plasma cells. To determine the phenotype and functional activity of Ig-secreting cells in human lymphoid tissue, we used a tonsillar organ culture model. A significant proportion of IgA and IgG secretion was shown to be mediated by long-lived, nonproliferating plasma cells that coexpressed high levels of CD27 and CD38. The presence of such cells was further corroborated by the finding of enhanced expression in the CD19(+) B-cell population of XBP-1, IRF-4, and particularly Blimp-1 genes involved in the differentiation of plasma cells. Intact tissue seemed to be necessary for optimal functional activity of plasma cells. A strong correlation was found between concentrations of interleukin-6 and IgA or IgG, but not IgM, in culture supernatants suggesting a role for interleukin-6 in the survival of long-lived plasma cells. Taken together, the present study demonstrates that human lymphoid tissue harbors a population of nonproliferating plasma cells that are dependent on an intact microenvironment for ongoing Ig secretion.
van Laar
Jacob M
JM
B Cell Biology Group, National Institute of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland, USA. j.m.van_laar@lumc.nl
Melchers
Marc
M
Teng
Y K Onno
YK
van der Zouwen
Boris
B
Mohammadi
Rozbeh
R
Fischer
Randy
R
Margolis
Leonid
L
Fitzgerald
Wendy
W
Grivel
Jean-Charles
JC
Breedveld
Ferdinand C
FC
Lipsky
Peter E
PE
Grammer
Amrie C
AC
D051997:ADP-ribosyl Cyclase 1 / Q000276:immunology; D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology; D002454:Cell Differentiation; D002469:Cell Separation; D016207:Cytokines / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D007070:Immunoglobulin A / Q000378:metabolism; D007136:Immunoglobulins / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism; D009924:Organ Culture Techniques; D014066:Palatine Tonsil / Q000166:cytology / Q000276:immunology; D010950:Plasma Cells / Q000276:immunology / Q000378:metabolism; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000276:immunology
D016207:Cytokines; D007070:Immunoglobulin A; D007136:Immunoglobulins; D015850:Interleukin-6; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D051997:ADP-ribosyl Cyclase 1
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