Accuri C6 Flow Cytometer System
Originally published online as doi:10.1189/jlb.0409268 on September 17, 2009

Published online before print September 17, 2009
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(Journal of Leukocyte Biology. 2009;86:1311-1318.)
© 2009 Society for Leukocyte Biology

IL-21 and IL-10 have redundant roles but differential capacities at different stages of plasma cell generation from human germinal center B cells

Sun-Ok Yoon1, Xin Zhang1, Paul Berner and Yong Sung Choi2

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

2. Correspondence: Laboratory of Cellular Immunology, 1514 Jefferson Highway, Ochsner Clinic Foundation, New Orleans, LA 70121, USA. E-mail: ychoi{at}ochsner.org

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.

Key Words: cytokines • cell differentiation