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Abstract:
SLP-65-/- mice display a partial block at the pre-B cell stage of development. Here, we show that LAT is required for the differentiation of SLP-65-/- pre-B cells. We show that LAT and SLP-76 are recruited to the pre-BCR and associated with Ig-α upon pre-BCR engagement, whereas LAT interaction with SLP-76 is already detected in untreated pre-B cells. Reconstitution of LAT or SLP-65 expression in SLP-65/LAT-/- pre-B cells restored their calcium (Ca2+ mobilization capacity, led to downregulation of surface pre-BCR, and induced differentiation to BCR+ cells. Together, our results suggest that the adaptor proteins LAT and SLP-76 are involved in pre-BCR signaling, thereby rescuing arrested murine SLP-65-/- pre-B cells.
