CROSS-LINKING OF THE IGM RECEPTOR INDUCES RAPID TRANSLOCATION OF IGM-ASSOCIATED IG-ALPHA, LYN, AND SYK TYROSINE KINASES TO THE MEMBRANE SKELETON

Cross-linking-induced association of membrane IgM (mlgM) with the cyto skeleton is well documented. However, its Functional significance duri ng B cell activation is not yet understood. One possible need for mlgM /cytoskeleton interactions may be to recruit the B cell receptor (BCR) -associated signaling molecules to the cytoskeletal matrix for the pro pagation of downstream signaling, We first verified whether BCR-associ ated Ig alpha translocates to the cytoskeleton together with mlgM in p olyclonal anti-IgM-treated murine B lymphoma cell line, BAL17.7.1. Go- capping experiments and the purification of the membrane skeleton unde r conditions that preserve IgM-Ig alpha beta interactions confirmed th at Ig alpha translocates to the cytoskeleton as part of the BCR comple x, Furthermore, two BCR-associated kinases that are known to play crit ical roles in anti-IgM-induced B cell signaling, the src Family kinase Lyn and the non-src family kinase Syk, accumulate in the membrane ske leton shortly after BCR cross-linking, when most of IgM and Ig alpha a ccumulate in this fraction, The kinetics of recruitment of the bulk of Ig alpha, Lyn, and Syk into the membrane skeleton appeared to precede the accumulation of their hypertyrosine-phosphorylated forms, suggest ing that activation of the BCR-associated signaling molecules occurs i n this fraction, These data suggest that cross-linked mlgM translocati ng to the membrane skeleton serves as a vehicle for active signaling m olecules to be recruited to this vicinity, This may promote B cell act ivation events by providing high affinity interactions between signali ng molecules and their substrates supported by the cytoskeletal matrix .