title: Antibodies against CD20 or B-cell receptor induce similar transcription patterns in human lymphoma cell lines.
abstract: BACKGROUND
  CD20 is a cell surface protein exclusively expressed on B cells. It is a clinically validated target for Non-Hodgkin's lymphomas (NHL) and autoimmune diseases. The B cell receptor (BCR) plays an important role for development and proliferation of pre-B and B cells. Physical interaction of CD20 with BCR and components of the BCR signaling cascade has been reported but the consequences are not fully understood.
  
  
  METHODS
  In this study we employed antibodies against CD20 and against the BCR to trigger the respective signaling. These antibodies induced very similar expression patterns of up- and down-regulated genes in NHL cell lines indicating that CD20 may play a role in BCR signaling and vice versa. Two of the genes that were rapidly and transiently induced by both stimuli are CCL3 and CCL4. 4 hours after stimulation the concentration of these chemokines in culture medium reaches a maximum. Spleen tyrosine kinase Syk is a cytoplasmic tyrosine kinase and a key component of BCR signaling. Both siRNA mediated silencing of Syk and inhibition by selective small molecule inhibitors impaired CCL3/CCL4 protein induction after treatment with either anti-CD20 or anti-BCR antibodies.
  
  
  CONCLUSIONS
  Our results suggest that treatment with anti-CD20 antibodies triggers at least partially a BCR activation-like response in NHL cell lines.
authors.affiliation: Pharma Research and Early Development, Roche Diagnostics GmbH, Penzberg, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Franke
authors.forename: Gerhard J
authors.initials: GJ
authors.lastname: Niederfellner
authors.forename: Christian
authors.initials: C
authors.lastname: Klein
authors.forename: Helmut
authors.initials: H
authors.lastname: Burtscher
mesh_terms: D000906:Antibodies / Q000494:pharmacology*; D058846:Antibodies, Monoclonal, Murine-Derived / Q000494:pharmacology; D018951:Antigens, CD20 / Q000276:immunology*; D045744:Cell Line, Tumor; D016000:Cluster Analysis; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D053263:Gene Regulatory Networks / Q000187:drug effects; D006801:Humans; D007074:Immunoglobulin G / Q000494:pharmacology; D007075:Immunoglobulin M / Q000494:pharmacology; D008228:Lymphoma, Non-Hodgkin / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D046228:Microarray Analysis; D011947:Receptors, Antigen, B-Cell / Q000037:antagonists & inhibitors / Q000276:immunology*; D000069283:Rituximab; D014158:Transcription, Genetic / Q000187:drug effects*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000906:Antibodies; D058846:Antibodies, Monoclonal, Murine-Derived; D018951:Antigens, CD20; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D011947:Receptors, Antigen, B-Cell; D000069283:Rituximab