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 (mIgM) with the cytoskeleton is well documented. However, its functional significance during B cell activation is not yet understood. One possible need for mIgM/cytoskeleton interactions may be to recruit the B cell receptor (BCR)-associated signaling molecules to the cytoskeletal matrix for the propagation of downstream signaling. We first verified whether BCR-associated Ig alpha translocates to the cytoskeleton together with mIgM in polyclonal anti-IgM-treated murine B lymphoma cell line, BAL17.7.1. Co-capping experiments and the purification of the membrane skeleton under conditions that preserve IgM-Ig alphabeta) interactions confirmed that Ig alpha translocates to the cytoskeleton as part of the BCR complex. Furthermore, two BCR-associated kinases that are known to play critical roles in anti-IgM-induced B cell signaling, the src family kinase Lyn and the non-src family kinase Syk, accumulate in the membrane skeleton shortly after BCR cross-linking, when most of IgM and Ig alpha accumulate 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, suggesting that activation of the BCR-associated signaling molecules occurs in this fraction. These data suggest that cross-linked mIgM translocating to the membrane skeleton serves as a vehicle for active signaling molecules to be recruited to this vicinity. This may promote B cell activation events by providing high affinity interactions between signaling molecules and their substrates supported by the cytoskeletal matrix.
Jugloff
L S
LS
Toronto Hospital Research Institute, Department of Immunology, University of Toronto, Ontario, Canada.
Jongstra-Bilen
J
J
D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D001692:Biological Transport / Q000276:immunology; D051925:CD79 Antigens; D002462:Cell Membrane / Q000201:enzymology / Q000276:immunology; D003599:Cytoskeleton / Q000201:enzymology* / Q000276:immunology; D004792:Enzyme Precursors / Q000276:immunology / Q000378:metabolism*; D007075:Immunoglobulin M / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins; D007700:Kinetics; D008213:Lymphocyte Activation; D051379:Mice; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000276:immunology / Q000378:metabolism*; D011947:Receptors, Antigen, B-Cell / Q000276:immunology / Q000378:metabolism*; D011961:Receptors, Fc / Q000378:metabolism*; D000072377:Syk Kinase; D019061:src-Family Kinases / Q000276:immunology / Q000378:metabolism*
D015703:Antigens, CD; D051925:CD79 Antigens; C497882:Cd79a protein, mouse; D004792:Enzyme Precursors; D007075:Immunoglobulin M; D047908:Intracellular Signaling Peptides and Proteins; D011947:Receptors, Antigen, B-Cell; D011961:Receptors, Fc; C035311:immunoglobulin M receptor; D019000:Phosphotyrosine; D011505:Protein-Tyrosine Kinases; D000072377:Syk Kinase; C000606897:Syk protein, mouse; C060902:lyn protein-tyrosine kinase; D019061:src-Family Kinases