CONTACT BETWEEN HUMAN BONE-MARROW STROMAL CELLS AND B-LYMPHOCYTES ENHANCES VERY LATE ANTIGEN-4 VASCULAR CELL-ADHESION MOLECULE-1-INDEPENDENT TYROSINE PHOSPHORYLATION OF FOCAL ADHESION KINASE, PAXILLIN, AND ERK2 IN STROMAL CELLS/

Contact with bone marrow stromal cells is crucial for the normal growt h and development of B-cell precursors, We have previously shown that human bone marrow stromal cell tyrosine kinase activity can be activat ed by direct contact with B-lymphoid cells (J Immunol 155:2359, 1995). In the present study, we show that increased tyrosine phosphorylation of focal adhesion kinase, paxillin, and extracellular-related kinase 2 (or p42 MAP kinase) accounted for the major changes occurring in str omal cell tyrosine phosphorylation after 5 to 10 minutes of contact wi th the RAMOS B-lymphoma cell line, Although adhesion of B-cell precurs ors to stromal cells is primarily mediated by very late antigen-4 (VLA -4) and vascular cell adhesion molecule-1 (VCAM-1), VLA-4-deficient an d adhesion-deficient RAMOS cells were equally capable of stimulating s tromal cell tyrosine phosphorylation. Similar changes in the tyrosine phosphorylation pattern of stromal cells were induced by contact with normal human B-cell precursors and several other B-lineage cell lines, After 5 to 30 minutes of contact with stromal cells, no change in pro tein tyrosine phosphorylation was detected in RAMOS or normal human B- cell precursors removed from stromal cells, Pretreatment of stromal ce lls with cytochalasin D abrogated contact-mediated enhancement of stro mal cell tyrosine phosphorylation, suggesting that an intact cytoskele ton was essential, These results suggest that B-cell contact activates stromal cell signaling cascades that regulate cytoskeletal organizati on and transcription, independent of the interaction mediated by VLA-4 and VCAM-1. (C) 1997 by The American Society of Hematology.