To understand how signals through CXCR4 are integrated via the IgD-BCR, scientists analyzed the activation of different signaling pathways, which are shared by both receptors. In B cells, the PI3K pathway is strongly regulated by CD19, which is localized in the vicinity of the IgD-BCR and IgM-BCR on resting and activated B cells, respectively. The expression of the IgD-BCR is required for the efficient phosphorylation of the PI3K downstream elements Akt and Foxo and Erk upon stimulation of B cells with either CXCL12 or Lat-A, suggesting that the cross-talk between CXCR4 and CD19 is BCR class dependent. The increased phosphorylation of Y182 of Igα also required IgD-BCR expression. These findings suggest that extensive actin depolymerization may represent a negative regulatory signal for the BCR.
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