Abstract

Intercellular adhesion molecule 1 (ICAM-1) (CD54) is an adhesion molecule of the immunoglobulin superfamily. The interaction between ICAM-1 on B lymphocytes and leukocyte function-associated antigen 1 on T cells plays a major role in several aspects of the immune response, including T-dependent B cell activation. While it was originally believed that ICAM-1 played a purely adhesive role, recent evidence suggests that it can itself transduce biochemical signals. We demonstrate that cross-linking of ICAM-1 results in the up-regulation of class II major histocompatibility complex, and we investigate the biochemical mechanism for the signaling role of ICAM-1. We show that cross-linking of ICAM-1 on the B lymphoma line A20 induces an increase in tyrosine phosphorylation of several cellular proteins, including the Src family kinase p53/p56(lyn). In vitro kinase assays showed that Lyn kinase was activated within 1 min after ICAM-1 cross-linking. In addition, ICAM-1 cross-linking resulted in activation of Raf-1 and mitogen-activated protein kinases, as determined by gel mobility shift. Activation of these kinases may represent important components in the cascade of signals that link ICAM-1 to various ICAM-1-elicited cellular responses. These data confirm the important role of ICAM-1 as a signaling molecule in B cell activation.