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Originally published online as doi:10.2353/ajpath.2007.070005 on August 9, 2007

Published online before print August 9, 2007
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(American Journal of Pathology. 2007;171:917-927.)
© 2007 American Society for Investigative Pathology
DOI: 10.2353/ajpath.2007.070005

Sustained Secretion of Immunoglobulin by Long-Lived Human Tonsil Plasma Cells

Jacob M. van Laar*{dagger}, Marc Melchers*{dagger}, Y. K. Onno Teng*{dagger}, Boris van der Zouwen*{dagger}, Rozbeh Mohammadi*{dagger}, Randy Fischer*, Leonid Margolis{ddagger}, Wendy Fitzgerald{ddagger}, Jean-Charles Grivel{ddagger}, Ferdinand C. Breedveld{dagger}, Peter E. Lipsky§ and Amrie C. Grammer*

From the B Cell Biology Group* and Autoimmunity Branch,§ National Institute of Musculoskeletal and Skin Diseases, and the Laboratory of Cellular and Molecular Biophysics,{ddagger} National Institute of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland; and the Department of Rheumatology,{dagger} Leiden University Medical Center, Leiden, The Netherlands

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.






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Copyright © 2007 by the American Society for Investigative Pathology.