Adhesion to fibronectin via alpha4 integrin (CD49d) protects B cells from apoptosis induced by serum deprivation but not via IgM or Fas/Apo-1 receptors.
Apoptosis is a regulated event crucial to the development and proliferation of normal and malignant B cells. We have studied the role of signals delivered via alpha4 integrin on apoptosis triggered by three different pathways on these cells. For apoptosis induced by serum deprivation, culturing B cells on the recombinant fibronectin fragment H89, a known ligand for alpha4beta1 integrin, resulted in statistically significant (P < 0.005) higher viability values (68%, 65% and 67%) for Ramos, Nalm-6 and EHEB cells, respectively, than culturing cells on poly lysine (42%, 42% and 48%). An antialpha4 MoAb reverted the protecting effect, thus confirming that it was due specifically to alpha4 engagement. Similarly, cells cultured on FN-III4-5, a recently identified fibronectin region which binds activated alpha4 integrin, also showed statistically significant higher viability than poly lysine cultures. Alpha4 engagement however, did not prevent apoptosis induced on Ramos cells via surface IgM. Adhesion of IM-9 cells, a myeloma cell line carrying functional Fas receptors, to the H89 fragment neither increased cell viability upon triggering apoptosis via Fas when compared to poly lysine. These results indicate that alpha4 signalling may overcome B cell apoptosis induced by the lack of growth factors but does not seem to affect the IgM or Fas apoptotic pathways, thus suggesting different intracellular mechanisms for these processes.
Garcia-Gila
M
M
Departamento de Inmunología, Centro de Investigaciones Biológicas, CSIC, Madrid, Spain.
Lopez-Martin
E M
EM
Garcia-Pardo
A
A
D015703:Antigens, CD / Q000378:metabolism*; D017209:Apoptosis; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002448:Cell Adhesion; D002460:Cell Line; D016895:Culture Media, Serum-Free; D019610:Cytoprotection; D005353:Fibronectins / Q000378:metabolism*; D006801:Humans; D007075:Immunoglobulin M / Q000276:immunology; D039441:Integrin alpha4; D039041:Integrin alpha4beta1; D016023:Integrins / Q000378:metabolism; D007700:Kinetics; D010446:Peptide Fragments / Q000378:metabolism; D018110:Receptors, Lipoprotein / Q000378:metabolism; D016201:Receptors, Lymphocyte Homing / Q000378:metabolism; D019014:fas Receptor / Q000378:metabolism
D015703:Antigens, CD; D016895:Culture Media, Serum-Free; C424122:FN-H89 fibronectin fragment; D005353:Fibronectins; D007075:Immunoglobulin M; D039041:Integrin alpha4beta1; D016023:Integrins; D010446:Peptide Fragments; D018110:Receptors, Lipoprotein; D016201:Receptors, Lymphocyte Homing; D019014:fas Receptor; D039441:Integrin alpha4