FRI0008 IL-21 regulates B cell proliferation and differentiation in rheumatoid arthritis

Deregulated expression of the Myc family of transcription factors (c-, N-, and L-myc) contributes to the development of many cancers by a mechanism believed to involve the stimulation of cell proliferation and inhibition of differentiation. However, using B cell–specific c-/N-myc double-knockout mice and Eμ-myc transgenic mice bred onto genetic backgrounds (recombinase-activating gene 2−/− and Btk−/− Tec−/−) whereby B cell development is arrested, we show that Myc is necessary to stimulate both proliferation and differentiation in primary B cells. Moreover, Myc expression results in sustained increases in intracellular Ca2+ ([Ca2+]i), which is required for Myc to stimulate B cell proliferation and differentiation. The increase in [Ca2+]i correlates with constitutive nuclear factor of activated T cells (NFAT) nuclear translocation, reduced Ca2+ efflux, and decreased expression of the plasma membrane Ca2+–adenosine triphosphatase (PMCA) efflux pump. Our findings demonstrate a revised model whereby Myc promotes both proliferation and differentiation, in part by a remarkable mechanism whereby Myc amplifies Ca2+ signals, thereby enabling the concurrent expression of Myc- and Ca2+-regulated target genes.

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Cleavage of membrane-bound CD40 ligand is not required for inducing B cell proliferation and differentiation

European Journal of Immunology ◽

10.1002/eji.1830260333 ◽

1996 ◽

Vol 26 (3) ◽

pp. 725-728 ◽

Cited By ~ 15

Author(s):

Fabienne Pietravalle ◽

Sybille Lecoanet-Henchoz ◽

Jean-Pierre Aubry ◽

Greg Elson ◽

Jean-Yves Bonnefoy ◽

...

Keyword(s):

Cell Proliferation ◽

B Cell ◽

Cd40 Ligand ◽

Cell Proliferation And Differentiation ◽

Proliferation And Differentiation ◽

Membrane Bound

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T-Cell Factors That Promote B-Cell Proliferation and Differentiation

The Interleukins ◽

10.1007/978-1-4684-4838-2_9 ◽

1985 ◽

pp. 219-229

Author(s):

Susan L. Swain ◽

Richard W. Dutton

Keyword(s):

Cell Proliferation ◽

T Cell ◽

B Cell ◽

Cell Proliferation And Differentiation ◽

Proliferation And Differentiation

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Induction of human B cell proliferation and differentiation by the combination of phorbol ester and ionomycin

European Journal of Immunology ◽

10.1002/eji.1830170519 ◽

1987 ◽

Vol 17 (5) ◽

pp. 701-706 ◽

Cited By ~ 9

Author(s):

Chaim M. Roifman ◽

Stephen H. Benedict ◽

Roy K. Cheung ◽

Erwin W. Gelfand

Keyword(s):

Cell Proliferation ◽

B Cell ◽

Phorbol Ester ◽

Cell Proliferation And Differentiation ◽

Proliferation And Differentiation ◽

Human B Cell

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The staphylococcal toxic shock syndrome toxin 1 triggers B cell proliferation and differentiation via major histocompatibility complex-unrestricted cognate T/B cell interaction.

Journal of Experimental Medicine ◽

10.1084/jem.170.6.2011 ◽

1989 ◽

Vol 170 (6) ◽

pp. 2011-2022 ◽

Cited By ~ 60

Author(s):

W Mourad ◽

P Scholl ◽

A Diaz ◽

R Geha ◽

T Chatila

Keyword(s):

Cell Proliferation ◽

B Cells ◽

B Cell ◽

Mhc Class Ii ◽

Cell Interaction ◽

Class Ii ◽

Toxic Shock ◽

Cell Proliferation And Differentiation ◽

Proliferation And Differentiation ◽

Toxic Shock Syndrome Toxin

The Staphylococcus aureus exotoxin toxic shock syndrome toxin 1 (TSST-1) is a potent activator of T cells and monocytes. We have recently demonstrated that TSST-1 is a superantigen that binds monomorphic determinants on MHC class II molecules. In the present study, we have examined the effect of TSST-1 on the activation and differentiation of high density human tonsillar B cells. TSST-1 bound to tonsilar B cells with high affinity and saturation kinetics. This binding was effectively inhibited by a combination of anti-HLA-DR and anti-HLA-DQ mAbs. Treatment of purified B cells with TSST-1 failed to induce B cell proliferation or Ig production. However, in the presence of irradiated T cells, TSST-1 induced resting B cells to proliferate and differentiate into Ig secretory cells. TSST-1 mimicked nominal antigen in that its induction of B cell responses was strictly dependent on physical contact between T and B cells, and was profoundly inhibited by anti-MHC class II mAbs, anti-CD3 mAbs, and, to a lesser extent, by anti-CD18 mAbs. However, unlike nominal antigen, TSST-1-mediated T/B cell interactions were MHC unrestricted. These results suggest that TSST-1 induces T cell-dependent B cell proliferation and differentiation by virtue of its ability to mediate MHC-unrestricted cognate T/B cell interaction via the TCR/CD3 complex and MHC class II antigens.

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