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Immunological synapse formation modulates affinity discrimination in Bcells
Author(s) -
Raychaudhuri Subhadip,
Tsourkas Phiippos,
Tolar Pavel
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1067.2
Subject(s) - immunological synapse , synapse , antigen , breakpoint cluster region , microbiology and biotechnology , b cell , cell , cell signaling , t cell , biophysics , chemistry , signal transduction , biology , receptor , t cell receptor , antibody , neuroscience , immune system , immunology , biochemistry
B cells are known to use their signaling mechanism to recognize antigens over a wide affinity range (10 6 – 10 10 M −1 ) and generate a graded response that depends on the affinity of antigen binding, a phenomenon known as affinity discrimination. Recent experiments have revealed that B cell signaling is crucially modulated through the immunological synapse ‐ an ordered protein segregation structure consisting of BCR/Antigen and LFA‐1/ICAM‐1 molecules that forms at the cell‐cell contact area. We have developed a Monte Carlo computer model to investigate whether synapse formation leads to differential B cell signaling upon ligation with antigens of varying affinity. For a given antigenic affinity, our numerical experiments give rise to stochastically varying levels of activated signaling molecules, such as phosphorylated BCR Igα/Igβ and Syk molecules, as observed in single cell experiments. Hence our model's stochastic nature can capture cell‐to‐cell stochastic fluctuations in B cell signaling. Based on our stochastic simulations we show that synapse formation modulates the B cell affinity discrimination. We also try to corroborate our computer simulation results with a simple mathematical model.