Figure 5.

Differences in Vav proteins, IL-10, and/or HSP70 expression between B-1a and B2 cells lead to the inability of B-1a cells to activate NF-κB and proliferate after BCR ligation. It is hypothesized that B-1a cells have increased levels or differential expression of phosphatases as compared to B2 cells, which could be at least partially the result of the increased basal expression of IL-10 and/or HSP70 seen in B-1a cells but not B2 cells. Furthermore, suboptimal Vav levels in B-1 cells (35) may not be sufficient for the production of ROS, which are necessary to inhibit phosphatases to allow activation of NF-κB after BCR ligation. Over-expression of the src kinase Lyn may also play a role in the non-response of B-1a cells to BCR ligation, perhaps by phosphorylation of inhibitory receptors. The mechanism through which Lyn contributes to B-1a cell non-responsiveness to BCR ligation is not clear; however, it has been demonstrated blocking Lyn activity can allow B-1a cells to respond to respond to BCR crosslinking.