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 lines that undergo spontaneous, lymphocyte function-associated antigen 1 (LFA-1) dependent homotypic adhesion in culture. This process is associated with induction of tyrosine phosphoproteins of molecular mass 90, 106, and 120 kDa and could be reproduced when these cells were centrifugationally aggregated. Antibodies to the beta 2 (CD18) chain of LFA-1 interfered with induction of p120, p106, and p90 during cellular aggregation. Response induction was abrogated when cells were incubated 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. Although the role of LFA-1-dependent tyrosine phosphorylation in B cells is 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.
Department of Medicine, UCLA School of Medicine, Center for the Health Sciences 90024-1680.
S C
SC
Wang
S B
SB
Kanner
J A
JA
Ledbetter
S
S
Gupta
G
G
Kumar
A E
AE
Nel
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001402:B-Lymphocytes / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D018821:CD18 Antigens / Q000276:immunology; D002448:Cell Adhesion / Q000502:physiology; D015815:Cell Adhesion Molecules / Q000502:physiology*; D002449:Cell Aggregation / Q000502:physiology; D002460:Cell Line; D003572:Cytochalasins / Q000494:pharmacology; D004854:Herpesvirus 4, Human; D006801:Humans; D016169:Lymphocyte Function-Associated Antigen-1 / Q000502:physiology*; D010750:Phosphoproteins / Q000096:biosynthesis / Q000378:metabolism*; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D014443:Tyrosine / Q000096:biosynthesis / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D018821:CD18 Antigens; D015815:Cell Adhesion Molecules; D003572:Cytochalasins; D016169:Lymphocyte Function-Associated Antigen-1; D010750:Phosphoproteins; C031582:cytochalasin C; D014443:Tyrosine; D011505:Protein-Tyrosine Kinases