Impairment of B cell receptor-mediated Ca2+ influx, activation of mitogen-activated protein kinases and growth inhibition in CD72-deficient BAL-17 cells

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Abstract
CD72 is a 45 kDa B cell‐specific type II transmembrane protein of the C‐type lectin superfamily. It was originally defined as a receptor‐like molecule that regulates B cell activation and differentiation; however, its precise function remains unclear since more recent functional analyses, including a gene targeting study, suggest that CD72 may serve as a negative or a positive regulator of B cell signaling. In the present study, we analyzed the cell‐autonomous function of CD72 in B cell receptor (BCR) signaling using CD72‐deficient cells generated from mature BAL‐17 cells. We found that BCR‐mediated phosphorylation of CD19, Btk, Vav and phospholipase Cγ2 and association of CD19 with phosphatidylinositol‐3 kinase were impaired in CD72‐deficient cells. Inositol trisphosphate synthesis was normally induced initially but ablated at 1 min of stimulation in CD72‐deficient cells. In the event, Ca2+ release from intracellular stores remained intact, though influx of extracellular Ca2+ was severely impaired in CD72‐deficient cells. Furthermore, BCR‐evoked activation of mitogen‐activated protein kinases (MAPKs), extracellular signal‐regulated kinase and c‐Jun NH2‐terminal kinase, and growth inhibition in BAL‐17 cells were blocked in the absence of CD72. Significantly, these effects were largely reversed by re‐expression of CD72. Thus, CD72 appears to exert a positive effect on BCR signaling pathways leading to Ca2+ influx and MAPK activation, which in turn may determine the fate of BAL‐17 cells.

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