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J Leukoc Biol. 2009 Dec;86(6):1311-8. doi: 10.1189/jlb.0409268. Epub 2009 Sep 17.

IL-21 and IL-10 have redundant roles but differential capacities at different stages of Plasma Cell generation from human Germinal Center B cells.

Author information

1
Laboratory of Cellular Immunology, Ochsner Clinic Foundation, New Orleans, Louisiana 70121, USA.

Abstract

The GC is the anatomical site where antigen-activated B cells differentiate into PC, producing high-affinity antibodies in physiological and pathological states. PC differentiation is regulated by multiple factors within the GC microenvironment, including cytokines. IL-21, a recently identified type I cytokine produced by GC-Th cells, promotes differentiation of human B cells into ISC. In this study, we investigated in detail the functional role of IL-21 in the course of GC-B cell differentiation into terminally differentiated PC compared with that of IL-10, a well-known PC differentiation factor. IL-21 had a greater capacity to initiate PC differentiation from CD77(+) centroblasts than IL-10 by strongly inducing PC transcription factors through activation of STAT3; however, IL-10 was more potent than IL-21 in generating CD138(+) PC from CD20(-)CD38(++) plasmablasts in the terminal stage of GC-B cell differentiation. This differential effect of IL-21 and IL-10 was reflected in receptor expression on B cell subsets emerging in the course of differentiation. Our studies have revealed that IL-21 is a critical decision-maker for driving initial PC differentiation at the stage of CD77(+) centroblasts, yet IL-10 is more effective in producing IgG by generating terminally differentiated CD138(+) PC at the later stage of PC differentiation in the GC.

PMID:
19762555
DOI:
10.1189/jlb.0409268
[Indexed for MEDLINE]

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