EVIDENCE FOR LFA-1 ICAM-1 DEPENDENT STIMULATION OF PROTEIN-TYROSINE PHOSPHORYLATION IN HUMAN-B LYMPHOID-CELL LINES DURING HOMOTYPIC ADHESION

JK32.1 and SKW6.4 are Epstein-Barr virus (EBV)-positive human B cell l ines that undergo spontaneous, lymphocyte function-associated antigen 1 (LFA-1) dependent homotypic adhesion in culture. This process is ass ociated with induction of tyrosine phosphoproteins of molecular mass 9 0, 106, and 120 kDa and could be reproduced when these cells were cent rifugationally aggregated. Antibodies to the beta(2) (CD18) chain of L FA-1 interfered with induction of p120, p106, and p90 during cellular aggregation. Response induction was abrogated when cells were incubate d with protein tyrosine kinase (PTK) inhibitors (erbstatin, genistein, and geldanomycin) or cytochalasin B prior to aggregation. An in vitro kinase assay did not reveal activation of focal adhesion kinase. Alth ough the role of LFA-1-dependent tyrosine phosphorylation in B cells i s uncertain, patients with the leukocyte adhesion defect (LAD) exhibit humoral abnormalities. Moreover, aggregation did not induce specific tyrosine phosphoproteins in an EBV-transformed B cell line from a LAD patient. These results suggest that an LFA-1-dependent PTK pathway may play an important role in human B cell function.