IL-21 and IL-10 have redundant roles but differential capacities at different stages of Plasma Cell generation from human Germinal Center B cells.
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.
Yoon
Sun-Ok
SO
Laboratory of Cellular Immunology, Ochsner Clinic Foundation, New Orleans, Louisiana 70121, USA.
Zhang
Xin
X
Berner
Paul
P
Choi
Yong Sung
YS
D015703:Antigens, CD / Q000276:immunology; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology*; D002478:Cells, Cultured; D005786:Gene Expression Regulation / Q000276:immunology; D018858:Germinal Center / Q000166:cytology / Q000276:immunology*; D006801:Humans; D016753:Interleukin-10 / Q000276:immunology*; D007378:Interleukins / Q000276:immunology*; D010950:Plasma Cells / Q000166:cytology / Q000276:immunology*; D050796:STAT3 Transcription Factor / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology / Q000276:immunology; D000098546:Interleukin-21
D015703:Antigens, CD; C508609:IL10 protein, human; D007378:Interleukins; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D016753:Interleukin-10; D000098546:Interleukin-21