The induction of antibody production by IL-6 is indirectly mediated by IL-21 produced by CD4+ T cells.

Interleukin (IL) 6 is a proinflammtory cytokine produced by antigen-presenting cells and nonhematopoietic cells in response to external stimuli. It was initially identified as a B cell growth factor and inducer of plasma cell differentiation in vitro and plays an important role in antibody production and class switching in vivo. However, it is not clear whether IL-6 directly affects B cells or acts through other mechanisms.

IP3 receptor-mediated Ca2+ release in naive CD4 T cells dictates their cytokine program.

IP(3) (inositol 1,4,5-trisphosphate) receptors (IP(3)Rs) regulate the release of Ca(2+) from intracellular stores in response to IP(3). Little is known about regulation of the expression of IP(3)Rs and their role during the activation of CD4 T cells. In this study we show that mouse naive CD4 T cells express IP(3)R1, IP(3)R2, and IP(3)R3, but that gene expression of IP(3)R3 primarily is down-regulated upon activation due to loss of the Ets-1 transcription factor.

Accumulation of NFAT mediates IL-2 expression in memory, but not naïve, CD4+ T cells.

In contrast to naïve CD4+ T cells, memory CD4+ T cells rapidly express high levels of effector cytokines in response to antigen stimulation. The molecular mechanism for this specific behavior is not well understood. The nuclear factor of activated T cells (NFAT) family of transcription factors plays an important role in the transcription of many cytokine genes.

Activation of p38 MAP kinase by DNA double-strand breaks in V(D)J recombination induces a G2/M cell cycle checkpoint.

Delay of cell cycle progression in response to double-strand DNA breaks (DSBs) is critical to allow time for DNA repair and prevent cellular transformation. Here, we show that the p38 mitogen-activated protein (MAP) kinase signaling pathway is activated in immature thymocytes along with TcRbeta gene V(D)J recombination. Active p38 MAP kinase promotes a G2/M cell cycle checkpoint through the phosphorylation and activation of p53 in these cells in vivo.