Abstract
BackgroundCD20 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.MethodologyIn 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.ConclusionOur results suggest that treatment with anti-CD20 antibodies triggers at least partially a BCR activation-like response in NHL cell lines.
Highlights
Activation of B cells is a tightly controlled process
Our results suggest that treatment with anti-CD20 antibodies triggers at least partially a B cell receptor (BCR) activation-like response in NonHodgkin’s lymphomas (NHL) cell lines
The cell lines used in this study (Z138, OciLy18, REC1 and SUDHL4) were all treated with both anti-IgM- and anti-IgG antibodies to trigger B cell receptor
Summary
One major component of these complex control mechanisms is the B cell antigen receptor (BCR) [1], a multimeric complex of membrane proteins with at least two immunoglobulin molecules together with CD79a/b in the core-unit and many accessory proteins [2]. In addition to ADCC and CDC, mediated via the Fc-part of an anti-CD20 antibody, mostly the so called type II anti-CD20 antibodies cause direct cell death by binding CD20 [6] - but the exact contribution of these different molecular mechanisms to efficacy is not yet fully understood [7,8]. CD20 is a cell surface protein exclusively expressed on B cells It is a clinically validated target for NonHodgkin’s lymphomas (NHL) and autoimmune diseases. Physical interaction of CD20 with BCR and components of the BCR signaling cascade has been reported but the consequences are not fully understood
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